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].
This course is open to students registered in the class only.
Please do not share or post course materials. This includes screenshots, audio, video, links, Zoom information, office hours, and recitations.
Team Assignments
Theta: James Gornet, Hristos Courellis, Jiahui Peng, Sita Gakkhar
Kappa: Pratyush Kandimalla, Tongtong Wang, James Guo, Manxuan Zhou
Lambda: Isabel D'Alessandro, Anastasiya Oguienko, Richard Horak
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.
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).
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: Lambda
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: Theta
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: Kappa
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: Kappa
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: Lambda
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: Theta
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.
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: Theta
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.
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: Lambda
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.
Slow waves, sharp waves, ripples, and REM in sleeping dragons
Authors: Mark Shein-Idelson, Janie M. Ondracek, Hua-Peng Liaw, Sam Reiter, Gilles Laurent
Journal: Science
Year: 2016
Group: Kappa
Abstract: Sleep has been described in animals ranging from worms to humans. Yet the electrophysiological characteristics of brain sleep, such as slow-wave (SW) and rapid eye movement (REM) activities, are thought to be restricted to mammals and birds. Recording from the brain of a lizard, the Australian dragon Pogona vitticeps, we identified SW and REM sleep patterns, thus pushing back the probable evolution of these dynamics at least to the emergence of amniotes. The SW and REM sleep patterns that we observed in lizards oscillated continuously for 6 to 10 hours with a period of ~80 seconds. The networks controlling SW-REM antagonism in amniotes may thus originate from a common, ancient oscillator circuit. Lizard SW dynamics closely resemble those observed in rodent hippocampal CA1, yet they originate from a brain area, the dorsal ventricular ridge, that has no obvious hodological similarity with the mammalian hippocampus.
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
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.
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.
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: Theta
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.
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: Lambda
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: Kappa
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: Theta
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.
Cortex-wide dynamics of intrinsic electrical activities: propagating waves and their interactions
Authors: Yuqi Liang, Chenchen Song, Mianxin Liu, Pulin Gong, Changsong Zhou and Thomas Knöpfel
Journal: Journal of Neuroscience
Year: 2021
Group: Lambda
Abstract: Intrinsic brain activities, as opposed to external stimulus-evoked responses, have increasingly gained attention, but it remains unclear how these intrinsic activities are spatiotemporally organized at the cortex-wide scale. By taking advantage of the high spatiotemporal resolution of optical voltage imaging, we identified five wave pattern types, and revealed the organization properties of different wave patterns and the dynamical mechanisms when they interact with each other. Moreover, we found a relationship between the emergence probability of local wave patterns and the multimodal structure hierarchy across cortical areas. Our findings reveal the principles of spatiotemporal wave dynamics of spontaneous activities and associate them with the underlying hierarchical architecture across 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: Lambda
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: Kappa
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.
Attractor dynamics in the hippocampal representation of the local environment
Authors: Tom J. Wills, Colin Lever, Francesca Cacucci, Neil Burgess, John O'Keefe
Journal: Science
Year: 2005
Group: Theta
Abstract: Memories are thought to be attractor states of neuronal representations, with the hippocampus a likely substrate for context-dependent episodic memories. However, such states have not been directly observed. For example, the hippocampal place cell representation of location was previously found to respond continuously to changes in environmental shape alone. We report that exposure to novel square and circular environments made of different materials creates attractor representations for both shapes: Place cells abruptly and simultaneously switch between representations as environmental shape changes incrementally. This enables study of attractor dynamics in a cognitive representation and may correspond to the formation of distinct contexts in context-dependent memory.
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: Kappa
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.
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: Theta
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.
Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation
Authors: André M. Bastos, Jacob A. Donoghue, Scott L. Brincat, Meredith Mahnke, Jorge Yanar, Josefina Correa, Ayan S. Waite, Mikael Lundqvist, Jefferson Roy, Emery N. Brown, Earl K. Miller
Journal: eLife
Year: 2021
Group: Lambda
Abstract: The specific circuit mechanisms through which anesthetics induce unconsciousness have not been completely characterized. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with the anesthetic propofol. Unconsciousness was marked by slow frequency (~1 Hz) oscillations in local field potentials, entrainment of local spiking to Up states alternating with Down states of little or no spiking activity, and decreased coherence in frequencies above 4 Hz. Thalamic stimulation ‘awakened’ anesthetized NHPs and reversed the electrophysiologic features of unconsciousness. Unconsciousness is linked to cortical and thalamic slow frequency synchrony coupled with decreased spiking, and loss of higher-frequency dynamics. This may disrupt cortical communication/integration.
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: Theta
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.
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: Lambda
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.
A distributional code for value in dopamine-based reinforcement learning
Authors: Will Dabney, Zeb Kurth-Nelson, Naoshige Uchida, Clara Kwon Starkweather, Demis Hassabis, Rémi Munos, and Matthew Botvinick
Journal: Nature
Year: 2020
Group: Kappa
Abstract: Since its introduction, the reward prediction error theory of dopamine has explained a wealth of empirical phenomena, providing a unifying framework for understanding the representation of reward and value in the brain. According to the now canonical theory, reward predictions are represented as a single scalar quantity, which supports learning about the expectation, or mean, of stochastic outcomes. Here we propose an account of dopamine-based reinforcement learning inspired by recent artificial intelligence research on distributional reinforcement learning. We hypothesized that the brain represents possible future rewards not as a single mean, but instead as a probability distribution, effectively representing multiple future outcomes simultaneously and in parallel. This idea implies a set of empirical predictions, which we tested using single-unit recordings from mouse ventral tegmental area. Our findings provide strong evidence for a neural realization of distributional reinforcement learning.