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 4th, 2018
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 11th, 2018
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: Kim-Marie Dam
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: Natalie Bernat and Dylan Bannon
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: Lily Zhang and Prashant Bhat
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: Lily Zhang and Natalie Bernat
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: Jeremy Bernstein and Prashant Bhat
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: Varun Wadia and Srinivas Chivukula
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 25th, 2018
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: Lily Zhang and Dylan Bannon
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.
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: Kim-Marie Dam and Jeremy Bernstein
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: Kim-Marie Dam and Jeremy Bernstein
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
Group: Natalie Bernat and Srinivas Chivukula
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.
The REM sleep–memory consolidation hypothesis
Authors: Jemore M. Siegel
Journal: Science
Year: 2001
Group: Prashant Bhat and Dylan Bannon
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.
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: Natalie Bernat and Kim-Marie Dam
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: Srinivas Chivukula and Lily Zhang
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.
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: Jeremy Bernstein
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: Lily Zhang and Kim-Marie Dam
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: Prashant Bhat and Srinivas Chivukula
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: Jeremy Bernstein and Lily Zhang
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: Natalie Bernat and Kim Dam
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: Dylan Bannon and Srinivas Chivukula
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 23rd, 2018
General anesthesia, sleep, and coma
Authors: Emery N. Brown, Ralph Lydic, and Nicholas D. Schiff
Journal: New England Journal of Medicine
Year: 2010
Group: Kim Dam and Prashant Bhat
Abstract: In the United States, nearly 60,000 patients per day receive general anesthesia for surgery. General anesthesia is a drug-induced, reversible condition that includes specific behavioral and physiological traits — unconsciousness, amnesia, analgesia, and akinesia — with concomitant stability of the autonomic, cardiovascular, respiratory, and thermoregulatory systems. General anesthesia produces distinct patterns on the electroencephalogram (EEG), the most common of which is a progressive increase in low-frequency, high-amplitude activity as the level of general anesthesia deepens. How anesthetic drugs induce and maintain the behavioral states of general anesthesia is an important question in medicine and neuroscience. Substantial insights can be gained by considering the relationship of general anesthesia to sleep and to coma.
Cortical and thalamic cellular correlates of electroencephalographic burst-suppression
Authors: M. Steriade, F. Amzica, and D. Contreras
Journal: Electroencephalography and Clinical Neurophysiology
Year: 1994
Group: Lily Zhang and Dylan Bannon
Abstract: This experimental study on anesthetized cats used intracellular recordings Of cortical, thalamocortical and reticular thalamic neurons (n = 54), as well as multi-site extracellular recordings (n = 36), to investigate the cellular correlates of EEG burst-suppression patterns, defined as alternating wave bursts and periods of electrical silence. Burst-suppression was elicited by the administration of the same or other anesthetic agents upon the background of an already synchronized EEG activity.
Local cortical dynamics of burst suppression in the anaesthetized brain
Authors: Laura D. Lewis, ShiNung Ching, Veronica S. Weiner, Robert A. Peterfreund, Emad N. Eskandar, Sydney S. Cash, Emery N. Brown, and Patrick L. Purdon
Journal: Brain
Year: 2013
Group: Jeremy Bernstein and Natalie Bernat
Abstract: Burst suppression is an electroencephalogram pattern that consists of a quasi-periodic alternation between isoelectric ‘suppressions’ lasting seconds or minutes, and high-voltage ‘bursts’. It is characteristic of a profoundly inactivated brain, occurring in conditions including hypothermia, deep general anaesthesia, infant encephalopathy and coma. It is also used in neurology as an electrophysiological endpoint in pharmacologically induced coma for brain protection after traumatic injury and during status epilepticus. Classically, burst suppression has been regarded as a ‘global’ state with synchronous activity throughout cortex. This assumption has influenced the clinical use of burst suppression as a way to broadly reduce neural activity. However, the extent of spatial homogeneity has not been fully explored due to the challenges in recording from multiple cortical sites simultaneously. The neurophysiological dynamics of large-scale cortical circuits during burst suppression are therefore not well understood. To address this question, we recorded intracranial electrocorticograms from patients who entered burst suppression while receiving propofol general anaesthesia. The electrodes were broadly distributed across cortex, enabling us to examine both the dynamics of burst suppression within local cortical regions and larger-scale network interactions. We found that in contrast to previous characterizations, bursts could be substantially asynchronous across the cortex. Furthermore, the state of burst suppression itself could occur in a limited cortical region while other areas exhibited ongoing continuous activity. In addition, we found a complex temporal structure within bursts, which recapitulated the spectral dynamics of the state preceding burst suppression, and evolved throughout the course of a single burst. Our observations imply that local cortical dynamics are not homogeneous, even during significant brain inactivation. Instead, cortical and, implicitly, subcortical circuits express seemingly different sensitivities to high doses of anaesthetics that suggest a hierarchy governing how the brain enters burst suppression, and emphasize the role of local dynamics in what has previously been regarded as a global state. These findings suggest a conceptual shift in how neurologists could assess the brain function of patients undergoing burst suppression. First, analysing spatial variation in burst suppression could provide insight into the circuit dysfunction underlying a given pathology, and could improve monitoring of medically-induced coma. Second, analysing the temporal dynamics within a burst could help assess the underlying brain state. This approach could be explored as a prognostic tool for recovery from coma, and for guiding treatment of status epilepticus. Overall, these results suggest new research directions and methods that could improve patient monitoring in clinical practice.
Class Date: May 30th, 2018
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: Natalie Bernat, Dylan Bannon, and Srinivas Chivukula
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.
The "wake-sleep" algorithm for unsupervised neural networks
Authors: Geoffrey E. Hinton, Peter Dayan, Brendan J. Frey, and Radford M. Neal
Journal: Science
Year: 1995
Group: Jeremy Bernstein and Kim Dam
Abstract: An unsupervised learning algorithm for a multilayer network of stochastic neurons is described. Bottom-up "recognition" connections convert the input into representations in successive hidden layers, and top-down "generative" connections reconstruct the representation in one layer from the representation in the layer above. In the "wake" phase, neurons are driven by recognition connections, and generative connections are adapted to increase the probability that they would reconstruct the correct activity vector in the layer below. In the "sleep" phase, neurons are driven by generative connections, and recognition connections are adapted to increase the probability that they would produce the correct activity vector in the layer above.
A neural algorithm for a fundamental computing problem
Authors: Sanjoy Dasgupta, Charles F. Stevens, and Saket Navlakha
Journal: Science
Year: 2017
Group: Lily Zhang and Prashant Bhat
Abstract: Similarity search—for example, identifying similar images in a database or similar documents on the web—is a fundamental computing problem faced by large-scale information retrieval systems. We discovered that the fruit fly olfactory circuit solves this problem with a variant of a computer science algorithm (called locality-sensitive hashing). The fly circuit assigns similar neural activity patterns to similar odors, so that behaviors learned from one odor can be applied when a similar odor is experienced. The fly algorithm, however, uses three computational strategies that depart from traditional approaches. These strategies can be translated to improve the performance of computational similarity searches. This perspective helps illuminate the logic supporting an important sensory function and provides a conceptually new algorithm for solving a fundamental computational problem.
Class Date: June 6th, 2018
Group 1: Dylan Bannon, Srinivas Chivukula, Prashant Bhat, and Kim Dam
Group 2: Natalie Bernat, Lily Zhang, and Jeremy Bernstein