The class focuses on quantitative studies of problems in systems neuroscience. Topics will include lateral inhibition, mechanisms of motion tuning, local learning rules and their consequences for network structure and dynamics, oscillatory dynamics and synchronization across brain circuits, and formation and computational properties of topographic neural maps. The course will combine discussions and presentations, in which students and faculty will examine and present papers on systems neuroscience, usually combining experimental and theoretical/modeling components. Example student presentation are included here [1], [2].
Class Date: April 3rd, 2019
From overshoot to voltage clamp
Authors: Andrew F. Huxley
Journal: Trends in Neurosciences
Year: 2002
Abstract: In 1939, A.L. Hodgkin and I found that the nerve action potential shows an ‘overshoot’ – that is, the interior of the fibre becomes electrically positive during an action potential. In 1948, we did our first experiments with a voltage clamp to investigate the current–voltage relations of the nerve membrane. Between those dates, we spent much time speculating about the mechanism by which ions cross the membrane and how the action potential is generated. This article summarizes these speculations, none of which has been previously published.
The Squid and its Giant Nerve Fiber
Excerpts from the film The Squid and its Giant Nerve Fiber, rehosted from Biological Sciences 300/301 at Smith College.
Electric impedance of the squid giant axon during activity
Authors: Kenneth S. Cole and Howard J. Curtis
Journal: Journal of General Physiology
Year: 1939
Abstract: Alternating current impedance measurements have been made over a wide frequency range on the giant axon from the stellar nerve of the squid, Loligo pealii, during the passage of a nerve impulse. The transverse impedance was measured between narrow electrodes on either side of the axon with a Wheatstone bridge having an amplifier and cathode ray oscillograph for detector. When the bridge was balanced, the resting axon gave a narrow line on the oscillograph screen as a sweep circuit moved the spot across. As an impulse passed between impedance electrodes after the axon had been stimulated at one end, the oscillograph line first broadened into a band, indicating a bridge unbalance, and then narrowed down to balance during recovery. From measurements made during the passage of the impulse and appropriate analysis, it was found that the membrane phase angle was unchanged, the membrane capacity decreased about two per cent, while the membrane conductance fell from a resting value of 1000 ohm cm2 to an average of twenty five ohm cm2.
The onset of the resistance change occurs somewhat after the start of the monophasic action potential, but coincides quite closely with the point of inflection on the rising phase, where the membrane current reverses in direction, corresponding to a decrease in the membrane electromotive force. This E.M.F. and the conductance are closely associated properties of the membrane, and their sudden changes constitute, or are due to, the activity which is responsible for the all-or-none law and the initiation and propagation of the nerve impulse. These results correspond to those previously found for Nitella and lead us to expect similar phenomena in other nerve fibers.
Measurement of current-voltage relations in the membrane of the giant axon of Loligo
Authors: Alan L. Hodgkin, Andrew F. Huxley, and Bernard Katz
Journal: Journal of Physiology
Year: 1952
Abstract: The importance of ionic movements in excitable tissues has been emphasized by a number of recent experiments. On the one hand, there is the finding that the nervous impulse is associated with an inflow of sodium and an outflow of potassiuim (eg Rothenberg, 1950; Keynes & Lewis, 1951). On the other, there are experiments which show that the rate of rise and amplitude of the action potential are determined by the concentration of sodium in the external medium (eg Hodgkin & Katz, 1949a; Huxley & Stiimpffi, 1951). Both groups of experiments are consistent with the theory that nervous conduction depends on a specific increase in permeability which allows sodium ions to move from the more concentrated solution outside a nerve fibre to the more dilute solution inside it. This movement of charge makes the inside of the fibre positive and provides a satisfactory explanation for the rising phase of the spike. Repolarization during the falling phase probably depends on an outflow of potassium ions and may be accelerated by a process which increases the potassium permeability after the action potential has reached its crest (Hodgkin, Huxley & Katz, 1949).
Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo
Authors: Alan L. Hodgkin and Andrew F. Huxley
Journal: Journal of Physiology
Year: 1952
Abstract: In the preceding paper (Hodgkin, Huxley & Katz, 1952) we gave a general description of the time course of the current which flows through the membrane of the squid giant axon when the potential difference across the membrane is suddenly changed from its resting value, and held at the new level by a feed-back circuit ('voltage clamp' procedure). This article is chiefly concerned with the identity of the ions which carry the various phases of the membrane current.
The components of membrane conductance in the giant axon of Loligo
Authors: Alan L. Hodgkin and Andrew F. Huxley
Journal: Journal of Physiology
Year: 1952
Abstract: The flow of current associated with depolarizations of the giant axon of Loligo has been described in two previous papers (Hodgkin, Huxley & Katz, 1952; Hodgkin & Huxley, 1952). These experiments were concerned with the effect of sudden displacements of the membrane potential from its resting level (V = 0) to a new level (V = Vj). This paper describes the converse situation in which the membrane potential is suddenly restored from V = V1 to V = 0. It also deals with certain aspects of the more general case in which V is changed suddenly from V1 to a new value V2. The experiments may be conveniently divided into those in which the period of depolarization is brief compared to the time scale of the nerve and those in which it is relatively long. The first group is largely concerned with movements of sodium ions and the second with movements of potassium ions.
The dual effect of membrane potential on sodium conductance in the giant axon of Loligo
Authors: Alan L. Hodgkin and Andrew F. Huxley
Journal: Journal of Physiology
Year: 1952
Abstract: This paper contains a further account of the electrical properties of the giant axon of Loligo. It deals with the 'inactivation' process which gradually reduces sodium permeability after it has undergone the initial rise associated with depolarization. Experiments described previously (Hodgkin & Huxley, 1952a, b) show that the sodium conductance always declines from its initial maximum, but they leave a number of important points unresolved. Thus they give no information about the rate at which repolarization restores the ability of the membrane to respond with its characteristic increase of sodium conductance. Nor do they provide much quantitative evidence about the influence of membrane potential on the process responsible for inactivation. These are the main problems with which this paper is concerned. The experimental method needs no special description, since it was essentially the same as that used previously (Hodgkin, Huiley & Katz, 1952; Hodgkin & Huxley, 1952b).
A quantitative description of membrane current and its application to conduction and excitation in nerve
Authors: Alan L. Hodgkin and Andrew F. Huxley
Journal: Journal of Physiology
Year: 1952
Abstract: This article concludes a series of papers concerned with the flow of electric current through the surface membrane of a giant nerve fibre (Hodgkin, Huxley & Katz, 1952; Hodgkin & Huxley, 1952 a-c). Its general object is to discuss the results of the preceding papers (Part I), to put them into mathematical form (Part II) and to show that they will account for conduction and excitation in quantitative terms (Part III).
Class Date: April 10th, 2019
Regulation of Synaptic Efficacy by Coincidence of Postsynaptic APs and EPSPs
Authors: Henry Markram, Joachim Lubke, Michael Frotscher, and Bert Sakmann
Journal: Science
Year: 1997
Group: Gamma
Abstract: Activity-driven modifications in synaptic connections between neurons in the neocortex may occur during development and learning. In dual whole-cell voltage recordings from pyramidal neurons, the coincidence of postsynaptic action potentials (APs) and unitary excitatory postsynaptic potentials (EPSPs) was found to induce changes in EPSPs. Their average amplitudes were differentially up- or down-regulated, depending on the precise timing of postsynaptic APs relative to EPSPs. These observations suggest that APs propagating back into dendrites serve to modify single active synaptic connections, depending on the pattern of electrical activity in the pre- and postsynaptic neurons.
Hebbian STDP in mushroom bodies facilitates the synchronous flow of olfactory information in locusts
Authors: Stijn Cassenaer and Gilles Laurent
Journal: Nature
Year: 2007
Group: Beta
Abstract: Odour representations in insects undergo progressive transformations and decorrelation from the receptor array to the presumed site of odour learning, the mushroom body. There, odours are represented by sparse assemblies of Kenyon cells in a large population. Using intracellular recordings in vivo, we examined transmission and plasticity at the synapse made by Kenyon cells onto downstream targets in locusts. We find that these individual synapses are excitatory and undergo hebbian spike-timing dependent plasticity (STDP) on a +/-25 ms timescale. When placed in the context of odour-evoked Kenyon cell activity (a 20-Hz oscillatory population discharge), this form of STDP enhances the synchronization of the Kenyon cells’ targets and thus helps preserve the propagation of the odour-specific codes through the olfactory system.
Conditional modulation of spike-timing-dependent plasticity for olfactory learning
Authors: Stijn Cassenaer and Gilles Laurent
Journal: Nature
Year: 2012
Group: Alpha
Abstract: Mushroom bodies are a well-known site for associative learning in insects. Yet the precise mechanisms that underlie plasticity there and ensure their specificity remain elusive. In locusts, the synapses between the intrinsic mushroom body neurons and their postsynaptic targets obey a Hebbian spike-timing-dependent plasticity (STDP) rule. Although this property homeostatically regulates the timing of mushroom body output, its potential role in associative learning is unknown. Here we show in vivo that pre–post pairing causing STDP can, when followed by the local delivery of a reinforcement-mediating neuromodulator, specify the synapses that will undergo an associative change. At these synapses, and there only, the change is a transformation of the STDP rule itself. These results illustrate the multiple actions of STDP, including a role in associative learning, despite potential temporal dissociation between the pairings that specify synaptic modification and the delivery of reinforcement-mediating neuromodulator signals.
Phase relationship between hippocampal place units and the EEG theta rhythm
Authors: John O'Keefe and Michael L. Recce
Journal: Hippocampus
Year: 1993
Group: Beta
Abstract: Many complex spike cells in the hippocampus of the freely moving rat have as their primary correlate the animal's location in an environment (place cells). In contrast, the hippocampal electroer cephalograph theta pattern of rhythmical waves (7–12 Hz) is better correlated with a class of movements that change the rat's location in an environment. During movement through the place field, the complex spike cells often fire in a bursting pattern with an interburst frequency in the same range as the concurrent electroencephalograph theta. The present study examined the phase of the theta wave at which the place cells fired. It was found that firing consistently began at a particular phase as the rat entered the field but then shifted in a systematic way during traversal of the field, moving progressively forward on each theta cycle. This precession of the phase ranged from 100° to 355° in different cells. The effect appeared to be due to the fact that individual cells had a higher interburst rate than the theta frequency. The phase was highly correlated with spatial location and less well correlated with temporal aspects of behavior, such as the time after place field entry. These results have implications for several aspects of hippocampal function. First, by using the phase relationship as well as the firing rate, place cells can improve the accuracy of place coding. Second, the characteristics of the phase shift constrain the models that define the construction of place fields. Third, the results restrict the temporal and spatial circumstances under which synapses in the hippocampus could be modified.
Large environments reveal the statistical structure governing hippocampal representations
Authors: P. Dylan Rich, Hua-Peng Liaw, and Albert K. Lee
Journal: Science
Year: 2014
Group: Alpha
Abstract: The rules governing the formation of spatial maps in the hippocampus have not been determined. We investigated the large-scale structure of place field activity by recording hippocampal neurons in rats exploring a previously unencountered 48-meter-long track. Single-cell and population activities were well described by a two-parameter stochastic model. Individual neurons had their own characteristic propensity for forming fields randomly along the track, with some cells expressing many fields and many exhibiting few or none. Because of the particular distribution of propensities across cells, the number of neurons with fields scaled logarithmically with track length over a wide, ethological range. These features constrain hippocampal memory mechanisms, may allow efficient encoding of environments and experiences of vastly different extents and durations, and could reflect general principles of population coding.
Behavioral time scale synaptic plasticity underlies CA1 place fields
Authors: Katie C. Bittner, Aaron D. Milstein, Christine Grienberger, Sandro Romani, and Jeffrey C. Magee
Journal: Science
Year: 2017
Group: Gamma
Abstract: Learning is primarily mediated by activity-dependent modifications of synaptic strength within neuronal circuits. We discovered that place fields in hippocampal area CA1 are produced by a synaptic potentiation notably different from Hebbian plasticity. Place fields could be produced in vivo in a single trial by potentiation of input that arrived seconds before and after complex spiking. The potentiated synaptic input was not initially coincident with action potentials or depolarization.This rule, named behavioral time scale synaptic plasticity, abruptly modifies inputs that were neither causal nor close in time to postsynaptic activation. In slices, five pairings of subthreshold presynaptic activity and calcium (Ca2+) plateau potentials produced a large potentiation with an asymmetric seconds-long time course. This plasticity efficiently stores entire behavioral sequences within synaptic weights to produce predictive place cell activity.
Class Date: April 24th, 2019
Reverse replay of behavioural sequences in hippocampal place cells during the awake state
Authors: David J. Foster and Matthew A. Wilson
Journal: Nature
Year: 2006
Group: Beta
Abstract: The hippocampus has long been known to be involved in spatial navigational learning in rodents, and in memory for events in rodents, primates and humans. A unifying property of both navigation and event memory is a requirement for dealing with temporally sequenced information. Reactivation of temporally sequenced memories for previous behavioural experiences has been reported in sleep in rats. Here we report that sequential replay occurs in the rat hippocampus during awake periods immediately after spatial experience. This replay has a unique form, in which recent episodes of spatial experience are replayed in a temporally reversed order. This replay is suggestive of a role in the evaluation of event sequences in the manner of reinforcement learning models. We propose that such replay might constitute a general mechanism of learning and memory.
Hippocampal reactivation of random trajectories resembling Brownian diffusion
Authors: Federico Stella, Peter Baracskay, Joseph O'Neill, and Jozsef Csicsvari
Journal: Neuron
Year: 2019
Group: Gamma
Abstract: Hippocampal activity patterns representing movement trajectories are reactivated in immobility and sleep periods, a process associated with memory recall, consolidation, and decision making. It is thought that only fixed, behaviorally relevant patterns can be reactivated, which are stored across hippocampal synaptic connections. To test whether some generalized rules govern reactivation, we examined trajectory reactivation following non-stereotypical exploration of familiar open-field environments. We found that random trajectories of varying lengths and timescales were reactivated, resembling that of Brownian motion of particles. The animals' behavioral trajectory did not follow Brownian diffusion demonstrating that the exact behavioral experience is not reactivated. Therefore, hippocampal circuits are able to generate random trajectories of any recently active map by following diffusion dynamics. This ability of hippocampal circuits to generate representations of all behavioral outcome combinations, experienced or not, may underlie a wide variety of hippocampal-dependent cognitive functions such as learning, generalization, and planning.
Selective suppression of hippocampal ripples impairs spatial memory
Authors: Gabrielle Girardeau, Karim Benchenane, Sidney I. Wiener, György Buzsáki, and Michaël B. Zugaro
Journal: Nature Neuroscience
Year: 2009
Group: Alpha
Abstract: Sharp wave–ripple (SPW-R) complexes in the hippocampus-entorhinal cortex are believed to be important for transferring labile memories from the hippocampus to the neocortex for long-term storage. We found that selective elimination of SPW-Rs during post-training consolidation periods resulted in performance impairment in rats trained on a hippocampus-dependent spatial memory task. Our results provide evidence for a prominent role of hippocampal SPW-Rs in memory consolidation.
Awake hippocampal sharp-wave ripples support spatial memory
Authors: Shantanu P. Jadhav, Caleb Kemere, P. Walter German, and Loren M. Frank
Journal: Science
Year: 2012
Group: Alpha
Abstract: The hippocampus is critical for spatial learning and memory. Hippocampal neurons in awake animals exhibit place field activity that encodes current location, and sharp-wave ripple (SWR) activity during which representations based on past experiences are often replayed. The relationship between these patterns of activity and the memory functions of the hippocampus is poorly understood. We interrupted awake SWRs in animals learning a spatial alternation task. We observed a specific learning and performance deficit that persisted throughout training. This deficit was associated with awake SWR activity as SWR interruption left place field activity and post-experience SWR reactivation intact. These results provide a link between awake SWRs and hippocampal memory processes, and suggest that awake replay of memory-related information during SWRs supports learning and memory-guided decision-making.
Hippocampal ripples down-regulate synapses
Authors: Hiroaki Norimoto, Kenichi Makino, Mengxuan Gao, Yu Shikano, Kazuki Okamoto, Tomoe Ishikawa, Takuya Sasaki, Hiroyuki Hioki, Shigeyoshi Fujisawa, and Yuji Ikegaya
Journal: Science
Year: 2018
Abstract: The specific effects of sleep on synaptic plasticity remain unclear. We report that mouse hippocampal sharp-wave ripple oscillations serve as intrinsic events that trigger long-lasting synaptic depression. Silencing of sharp-wave ripples during slow-wave states prevented the spontaneous down-regulation of net synaptic weights and impaired the learning of new memories. The synaptic down-regulation was dependent on the N-methyl-d-aspartate receptor and selective for a specific input pathway. Thus, our findings are consistent with the role of slow-wave states in refining memory engrams by reducing recent memory-irrelevant neuronal activity and suggest a previously unrecognized function for sharp-wave ripples.
Class Date: May 1st, 2019
Neuronal ensembles sufficient for recovery sleep and the sedative actions of α2 adrenergic agonists
Authors: Zhe Zhang, Valentina Ferretti, İlke Güntan, Alessandro Moro, Eleonora A. Steinberg, Zhiwen Ye, Anna Y. Zecharia, Xiao Yu, Alexei L. Vyssotski, Stephen G. Brickley, Raquel Yustos, Zoe E. Pillidge, Edward C. Harding, William Wisden, and Nicholas P. Franks
Journal: Nature Neuroscience
Year: 2015
Group: Beta
Abstract: Do sedatives engage natural sleep pathways? It is usually assumed that anesthetic-induced sedation and loss of righting reflex (LORR) arise by influencing the same circuitry to lesser or greater extents. For the α2 adrenergic receptor agonist dexmedetomidine, we found that sedation and LORR were in fact distinct states, requiring different brain areas: the preoptic hypothalamic area and locus coeruleus (LC), respectively. Selective knockdown of α2A adrenergic receptors from the LC abolished dexmedetomidine-induced LORR, but not sedation. Instead, we found that dexmedetomidine-induced sedation resembled the deep recovery sleep that follows sleep deprivation. We used TetTag pharmacogenetics in mice to functionally mark neurons activated in the preoptic hypothalamus during dexmedetomidine-induced sedation or recovery sleep. The neuronal ensembles could then be selectively reactivated. In both cases, non-rapid eye movement sleep, with the accompanying drop in body temperature, was recapitulated. Thus, α2 adrenergic receptor–induced sedation and recovery sleep share hypothalamic circuitry sufficient for producing these behavioral states.
Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness
Authors: Francisco J. Flores, Katharine E. Hartnack, Amanda B. Fath, Seong-Eun Kim, Matthew A. Wilson, Emery N. Brown, and Patrick L. Purdon
Journal: Proceedings of the National Academy of Sciences
Year: 2017
Group: Alpha
Abstract: General anesthesia is a drug-induced state of altered arousal associated with profound, stereotyped electrophysiological oscillations. Here we report evidence in rats that propofol, an anesthetic drug frequently used in clinical practice, disrupts activity in medial prefrontal cortex and thalamus by inducing highly synchronized oscillations between these structures. These oscillations closely parallel human electroencephalogram oscillations under propofol. Disruption of activity in medial prefrontal cortex by these oscillations implies an impairment of self-awareness and internal consciousness. During recovery of consciousness, these synchronized oscillations dissipate in a "boot-up" sequence most likely driven by ascending arousal centers. These studies advance our understanding of what it means to be unconscious under anesthesia and establish principled neurophysiological markers to monitor and manage this state.
A common neuroendocrine substrate for diverse general anesthetics and sleep
Authors: Li-Feng Jiang-Xie, Luping Yin, Shengli Zhao, Vincent Prevosto, Bao-Xia Han, Kafui Dzirasa, Fan Wang
Journal: Neuron
Year: 2019
Group: Gamma
Abstract: How general anesthesia (GA) induces loss of consciousness remains unclear, and whether diverse anesthetic drugs and sleep share a common neural pathway is unknown. Previous studies have revealed that many GA drugs inhibit neural activity through targeting GABA receptors. Here, using Fos staining, ex vivo brain slice recording, and in vivo multi-channel electrophysiology, we discovered a core ensemble of hypothalamic neurons in and near the supraoptic nucleus, consisting primarily of neuroendocrine cells, which are persistently and commonly activated by multiple classes of GA drugs. Remarkably, chemogenetic or brief optogenetic activations of these anesthesia-activated neurons (AANs) strongly promote slow-wave sleep and potentiates GA, whereas conditional ablation or inhibition of AANs led to diminished slow-wave oscillation, significant loss of sleep, and shortened durations of GA. These findings identify a common neural substrate underlying diverse GA drugs and natural sleep and reveal a crucial role of the neuroendocrine system in regulating global brain states.
General anesthesia and altered states of arousal: a systems neuroscience analysis
Authors: Emery N. Brown, Patrick L. Purdon, and Christa J. Van Dort
Journal: Annual Review of Neuroscience
Year: 2011
Abstract: Placing a patient in a state of general anesthesia is crucial for safely and humanely performing most surgical and many nonsurgical procedures. How anesthetic drugs create the state of general anesthesia is considered a major mystery of modern medicine. Unconsciousness, induced by altered arousal and/or cognition, is perhaps the most fascinating behavioral state of general anesthesia. We perform a systems neuroscience analysis of the altered arousal states induced by five classes of intravenous anesthetics by relating their behavioral and physiological features to the molecular targets and neural circuits at which these drugs are purported to act. The altered states of arousal are sedation-unconsciousness, sedation-analgesia, dissociative anesthesia, pharmacologic non-REM sleep, and neuroleptic anesthesia. Each altered arousal state results from the anesthetic drugs acting at multiple targets in the central nervous system. Our analysis shows that general anesthesia is less mysterious than currently believed.
Class Date: May 8th, 2019
Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep
Authors: Kenway Louie and Matthew A. Wilson
Journal: Neuron
Year: 2001
Group: Beta
Abstract: Human dreaming occurs during rapid eye movement (REM) sleep. To investigate the structure of neural activity during REM sleep, we simultaneously recorded the activity of multiple neurons in the rat hippocampus during both sleep and awake behavior. We show that temporally sequenced ensemble firing rate patterns reflecting tens of seconds to minutes of behavioral experience are reproduced during REM episodes at an equivalent timescale. Furthermore, within such REM episodes behavior-dependent modulation of the subcortically driven theta rhythm is also reproduced. These results demonstrate that long temporal sequences of patterned multineuronal activity suggestive of episodic memory traces are reactivated during REM sleep. Such reactivation may be important for memory processing and provides a basis for the electrophysiological examination of the content of dream states.
Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation
Authors: Richard Boyce, Stephen D. Glasgow, Sylvain Williams, and Antoine Adamantidis
Journal: Science
Year: 2016
Group: Alpha
Abstract: Rapid eye movement sleep (REMS) has been linked with spatial and emotional memory consolidation. However, establishing direct causality between neural activity during REMS and memory consolidation has proven difficult because of the transient nature of REMS and significant caveats associated with REMS deprivation techniques. In mice, we optogenetically silenced medial septum γ-aminobutyric acid–releasing (MSGABA) neurons, allowing for temporally precise attenuation of the memory-associated theta rhythm during REMS without disturbing sleeping behavior. REMS-specific optogenetic silencing of MSGABA neurons selectively during a REMS critical window after learning erased subsequent novel object place recognition and impaired fear-conditioned contextual memory. Silencing MSGABA neurons for similar durations outside REMS episodes had no effect on memory. These results demonstrate that MSGABA neuronal activity specifically during REMS is required for normal memory consolidation.
Control of REM sleep by ventral medulla GABAergic neurons
Authors: Franz Weber, Shinjae Chung, Kevin T. Beier, Min Xu, Liqun Luo, and Yang Dan
Journal: Nature
Year: 2015
Group: Gamma
Abstract: Rapid eye movement (REM) sleep is a distinct brain state characterized by activated electroencephalogram and complete skeletal muscle paralysis, and is associated with vivid dreams. Transection studies by Jouvet first demonstrated that the brainstem is both necessary and sufficient for REM sleep generation, and the neural circuits in the pons have since been studied extensively. The medulla also contains neurons that are active during REM sleep, but whether they play a causal role in REM sleep generation remains unclear. Here we show that a GABAergic (γ-aminobutyric-acid-releasing) pathway originating from the ventral medulla powerfully promotes REM sleep in mice. Optogenetic activation of ventral medulla GABAergic neurons rapidly and reliably initiated REM sleep episodes and prolonged their durations, whereas inactivating these neurons had the opposite effects. Optrode recordings from channelrhodopsin-2-tagged ventral medulla GABAergic neurons showed that they were most active during REM sleep (REMmax), and during wakefulness they were preferentially active during eating and grooming. Furthermore, dual retrograde tracing showed that the rostral projections to the pons and midbrain and caudal projections to the spinal cord originate from separate ventral medulla neuron populations. Activating the rostral GABAergic projections was sufficient for both the induction and maintenance of REM sleep, which are probably mediated in part by inhibition of REM-suppressing GABAergic neurons in the ventrolateral periaqueductal grey. These results identify a key component of the pontomedullary network controlling REM sleep. The capability to induce REM sleep on command may offer a powerful tool for investigating its functions.
The function of dream sleep
Authors: Francis Crick and Graeme Mitchison
Journal: Nature
Year: 1983
Abstract: We propose that the function of dream sleep (more properly rapid-eye movement or REM sleep) is to remove certain undesirable modes of interaction in networks of cells in the cerebral cortex. We postulate that this is done in REM sleep by a reverse learning mechanism, so that the trace in the brain of the unconscious dream is weakened, rather than strengthened, by the dream.
The REM sleep–memory consolidation hypothesis
Authors: Jemore M. Siegel
Journal: Science
Year: 2001
Abstract: It has been hypothesized that REM (rapid eye movement) sleep has an important role in memory consolidation. The evidence for this hypothesis is reviewed and found to be weak and contradictory. Animal studies correlating changes in REM sleep parameters with learning have produced inconsistent results and are confounded by stress effects. Humans with pharmacological and brain lesion–induced suppression of REM sleep do not show memory deficits, and other human sleep-learning studies have not produced consistent results. The time spent in REM sleep is not correlated with learning ability across humans, nor is there a positive relation between REM sleep time or intensity and encephalization across species. Although sleep is clearly important for optimum acquisition and performance of learned tasks, a major role in memory consolidation is unproven.
Traveling waves in developing cerebellar cortex mediated by asymmetrical Purkinje cell connectivity
Authors: Alanna J. Watt, Hermann Cuntz, Masahiro Mori, Zoltan Nusser, P. Jesper Sjöström, and Michael Häusser
Journal: Nature Neuroscience
Year: 2009
Group: Beta
Abstract: Correlated network activity is important in the development of many neural circuits. Purkinje cells are among the first neurons to populate the cerebellar cortex, where they sprout exuberant axon collaterals. We used multiple patch-clamp recordings targeted with two-photon microscopy to characterize monosynaptic connections between the Purkinje cells of juvenile mice. We found that Purkinje cell axon collaterals projected asymmetrically in the sagittal plane, directed away from the lobule apex. On the basis of our anatomical and physiological characterization of this connection, we constructed a network model that robustly generated waves of activity that traveled along chains of connected Purkinje cells. Consistent with the model, we observed traveling waves of activity in Purkinje cells in sagittal slices from young mice that require GABAA receptor–mediated transmission and intact Purkinje cell axon collaterals. These traveling waves are absent in adult mice, suggesting they have a developmental role in wiring the cerebellar cortical microcircuit.
Hippocampal theta oscillations are travelling waves
Authors: Evgueniy V. Lubenov and Athanassios G. Siapas
Journal: Nature
Year: 2009
Group: Gamma
Abstract: Theta oscillations clock hippocampal activity during awake behaviour and rapid eye movement (REM) sleep. These oscillations are prominent in the local field potential, and they also reflect the subthreshold membrane potential and strongly modulate the spiking of hippocampal neurons. The prevailing view is that theta oscillations are synchronized throughout the hippocampus, despite the lack of conclusive experimental evidence. In contrast, here we show that in freely behaving rats, theta oscillations in area CA1 are travelling waves that propagate roughly along the septotemporal axis of the hippocampus. Furthermore, we find that spiking in the CA1 pyramidal cell layer is modulated in a consistent travelling wave pattern. Our results demonstrate that theta oscillations pattern hippocampal activity not only in time, but also across anatomical space. The presence of travelling waves indicates that the instantaneous output of the hippocampus is topographically organized and represents a segment, rather than a point, of physical space.
Cortical travelling waves: mechanisms and computational principles
Authors: Lyle Muller, Frédéric Chavane, John Reynolds, and Terrence J. Sejnowski
Journal: Nature Reviews Neuroscience
Year: 2018
Group: Alpha
Abstract: Multichannel recording technologies have revealed travelling waves of neural activity in multiple sensory, motor and cognitive systems. These waves can be spontaneously generated by recurrent circuits or evoked by external stimuli. They travel along brain networks at multiple scales, transiently modulating spiking and excitability as they pass. Here, we review recent experimental findings that have found evidence for travelling waves at single-area (mesoscopic) and whole-brain (macroscopic) scales. We place these findings in the context of the current theoretical understanding of wave generation and propagation in recurrent networks. During the large low-frequency rhythms of sleep or the relatively desynchronized state of the awake cortex, travelling waves may serve a variety of functions, from long-term memory consolidation to processing of dynamic visual stimuli. We explore new avenues for experimental and computational understanding of the role of spatiotemporal activity patterns in the cortex.
Neural networks and physical systems with emergent collective computational abilities
Authors: John J. Hopfield
Journal: Proceedings of the National Academy of Sciences
Year: 1982
Group: Alpha
Abstract: Computational properties of use of biological organisms or to the construction of computers can emerge as collective properties of systems having a large number of simple equivalent components (or neurons). The physical meaning of content-addressable memory is described by an appropriate phase space flow of the state of a system. A model of such a system is given, based on aspects of neurobiology but readily adapted to integrated circuits. The collective properties of this model produce a content-addressable memory which correctly yields an entire memory from any subpart of sufficient size. The algorithm for the time evolution of the state of the system is based on asynchronous parallel processing. Additional emergent collective properties include some capacity for generalization, familiarity recognition, categorization, error correction, and time sequence retention. The collective properties are only weakly sensitive to details of the modeling or the failure of individual devices.
Synaptic mechanisms of pattern completion in the hippocampal CA3 network
Authors: Segundo Jose Guzman, Alois Schlögl, Michael Frotscher, and Peter Jonas
Journal: Science
Year: 2016
Group: Gamma
Abstract: The hippocampal CA3 region plays a key role in learning and memory. Recurrent CA3–CA3 synapses are thought to be the subcellular substrate of pattern completion. However, the synaptic mechanisms of this network computation remain enigmatic. To investigate these mechanisms, we combined functional connectivity analysis with network modeling. Simultaneous recording from up to eight CA3 pyramidal neurons revealed that connectivity was sparse, spatially uniform, and highly enriched in disynaptic motifs (reciprocal, convergence, divergence, and chain motifs). Unitary connections were composed of one or two synaptic contacts, suggesting efficient use of postsynaptic space. Real-size modeling indicated that CA3 networks with sparse connectivity, disynaptic motifs, and single-contact connections robustly generated pattern completion. Thus, macro- and microconnectivity contribute to efficient memory storage and retrieval in hippocampal networks.
Requirement for hippocampal CA3 NMDA receptors in associative memory recall
Authors: Kazu Nakazawa, Michael C. Quirk, Raymond A. Chitwood, Masahiko Watanabe, Mark F. Yeckel, Linus D. Sun, Akira Kato, Candice A. Carr, Daniel Johnston, Matthew A. Wilson, and Susumu Tonegawa
Journal: Science
Year: 2002
Group: Beta
Abstract: Pattern completion, the ability to retrieve complete memories on the basis of incomplete sets of cues, is a crucial function of biological memory systems. The extensive recurrent connectivity of the CA3 area of hippocampus has led to suggestions that it might provide this function. We have tested this hypothesis by generating and analyzing a genetically engineered mouse strain in which theN-methyl-d-asparate (NMDA) receptor gene is ablated specifically in the CA3 pyramidal cells of adult mice. The mutant mice normally acquired and retrieved spatial reference memory in the Morris water maze, but they were impaired in retrieving this memory when presented with a fraction of the original cues. Similarly, hippocampal CA1 pyramidal cells in mutant mice displayed normal place-related activity in a full-cue environment but showed a reduction in activity upon partial cue removal. These results provide direct evidence for CA3 NMDA receptor involvement in associative memory recall.
Class Date: May 29th, 2019
A framework for mesencephalic dopamine systems based on predictive Hebbian learning
Authors: P. Read Montague, Peter Dayan, and Terrence J. Sejnowski
Journal: Journal of Neuroscience
Year: 1996
Group: Beta
Abstract: We develop a theoretical framework that shows how mesencephalic dopamine systems could distribute to their targets a signal that represents information about future expectations. In particular, we show how activity in the cerebral cortex can make predictions about future receipt of reward and how fluctuations in the activity levels of neurons in diffuse dopamine systems above and below baseline levels would represent errors in these predictions that are delivered to cortical and subcortical targets. We present a model for how such errors could be constructed in a real brain that is consistent with physiological results for a subset of dopaminergic neurons located in the ventral tegmental area and surrounding dopaminergic neurons. The theory also makes testable predictions about human choice behavior on a simple decision-making task. Furthermore, we show that, through a simple influence on synaptic plasticity, fluctuations in dopamine release can act to change the predictions in an appropriate manner.
Prefrontal cortex as a meta-reinforcement learning system
Authors: Jane X. Wang, Zeb Kurth-Nelson, Dharshan Kumaran, Dhruva Tirumala, Hubert Soyer, Joel Z. Leibo, Demis Hassabis, and Matthew Botvinick
Journal: Nature Neuroscience
Year: 2018
Group: Alpha
Abstract: Over the past 20 years, neuroscience research on reward-based learning has converged on a canonical model, under which the neurotransmitter dopamine ‘stamps in’ associations between situations, actions and rewards by modulating the strength of synaptic connections between neurons. However, a growing number of recent findings have placed this standard model under strain. We now draw on recent advances in artificial intelligence to introduce a new theory of reward-based learning. Here, the dopamine system trains another part of the brain, the prefrontal cortex, to operate as its own free-standing learning system. This new perspective accommodates the findings that motivated the standard model, but also deals gracefully with a wider range of observations, providing a fresh foundation for future research.
Vector-based navigation using grid-like representations in artificial agents
Authors: Andrea Banino, Caswell Barry, Benigno Uria, Charles Blundell, Timothy Lillicrap, Piotr Mirowski, Alexander Pritzel, Martin J. Chadwick, Thomas Degris, Joseph Modayil, Greg Wayne, Hubert Soyer, Fabio Viola, Brian Zhang, Ross Goroshin, Neil Rabinowitz, Razvan Pascanu, Charlie Beattie, Stig Petersen, Amir Sadik, Stephen Gaffney, Helen King, Koray Kavukcuoglu, Demis Hassabis, Raia Hadsell, and Dharshan Kumaran
Journal: Nature
Year: 2018
Group: Gamma
Abstract: Deep neural networks have achieved impressive successes in fields ranging from object recognition to complex games such as Go. Navigation, however, remains a substantial challenge for artificial agents, with deep neural networks trained by reinforcement learning failing to rival the proficiency of mammalian spatial behaviour, which is underpinned by grid cells in the entorhinal cortex. Grid cells are thought to provide a multi-scale periodic representation that functions as a metric for coding space and is critical for integrating self-motion (path integration) and planning direct trajectories to goals (vector-based navigation). Here we set out to leverage the computational functions of grid cells to develop a deep reinforcement learning agent with mammal-like navigational abilities. We first trained a recurrent network to perform path integration, leading to the emergence of representations resembling grid cells, as well as other entorhinal cell types. We then showed that this representation provided an effective basis for an agent to locate goals in challenging, unfamiliar, and changeable environments—optimizing the primary objective of navigation through deep reinforcement learning. The performance of agents endowed with grid-like representations surpassed that of an expert human and comparison agents, with the metric quantities necessary for vector-based navigation derived from grid-like units within the network. Furthermore, grid-like representations enabled agents to conduct shortcut behaviours reminiscent of those performed by mammals. Our findings show that emergent grid-like representations furnish agents with a Euclidean spatial metric and associated vector operations, providing a foundation for proficient navigation. As such, our results support neuroscientific theories that see grid cells as critical for vector-based navigation, demonstrating that the latter can be combined with path-based strategies to support navigation in challenging environments.
Deep learning
Authors: Yann LeCun, Yoshua Bengio, and Geoffrey Hinton
Journal: Nature
Year: 2015
Abstract: Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech.
Reinforcement learning
Authors: Richard S. Sutton and Andrew G. Barto
Year: 2018
Abstract: The idea that we learn by interacting with our environment is probably the first to occur to us when we think about the nature of learning. When an infant plays, waves its arms,or looks about, it has no explicit teacher, but it does have a direct sensorimotor connection to its environment. Exercising this connection produces a wealth of information about cause and effect, about the consequences of actions, and about what to do in order to achieve goals. Throughout our lives, such interactions are undoubtedly a major source of knowledge about our environment and ourselves. Whether we are learning to drive a car or to hold a conversation, we are acutely aware of how our environment responds to what we do, and we seek to influence what happens through our behavior. Learning from interaction is a foundational idea underlying nearly all theories of learning and intelligence.
Class Date: June 5th, 2019 No class or final presentations