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.
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: Nicholas and Anthony
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: Nathaniel
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: Wongyo and Panagiota
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: Panagiota and Anthony
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: Wongyo
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.
Persistence of neuronal representations through time and damage in the hippocampus
Authors: Walter G. Gonzalez, Hanwen Zhang, Anna Harutyunyan, and Carlos Lois
Journal: Science
Year: 2019
Group: Nathaniel and Nicholas
Abstract: How do neurons encode long-term memories? Bilateral imaging of neuronal activity in the mouse hippocampus reveals that, from one day to the next, ~40% of neurons change their responsiveness to cues, but thereafter only 1% of cells change per day. Despite these changes, neuronal responses are resilient to a lack of exposure to apreviously completed task or to hippocampus lesions. Unlike individual neurons, the responses of which change after a few days, groups of neurons with inter- and intrahemispheric synchronous activity show stable responses for several weeks. The likelihood that a neuron maintains its responsiveness across days is proportional to the number of neurons with which its activity is synchronous. Information stored in individual neurons is relatively labile, but it can be reliably stored in networks of synchronously active neurons.
Optogenetic stimulation of a hippocampal engram activates fear memory recall
Authors: Xu Liu, Steve Ramirez, Petti T. Pang, Corey B. Puryear, Arvind Govindarajan, Karl Deisseroth, and Susumu Tonegawa
Journal: Nature
Year: 2012
Group: Nathaniel and Panagiota
Abstract: A specific memory is thought to be encoded by a sparse population of neurons. These neurons can be tagged during learning for subsequent identification and manipulation. Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour.
The hippocampal engram maps experience but not place
Authors: Kazumasa Z. Tanaka, Hongshen He, Anupratap Tomar, Kazue Niisato, Arthur J. Y. Huang, and Thomas J. McHugh
Journal: Science
Year: 2018
Group: Desi and Ange
Abstract: Episodic memories are encoded by a sparse population of hippocampal neurons. In mice, optogenetic manipulation of this memory engram established that these neurons are indispensable and inducing for memory recall. However, little is known about their in vivo activity or precise role in memory. We found that during memory encoding, only a fraction of CA1 place cells function as engram neurons, distinguished by firing repetitive bursts paced at the theta frequency. During memory recall, these neurons remained highly context specific, yet demonstrated preferential remapping of their place fields. These data demonstrate a dissociation of precise spatial coding and contextual indexing by distinct hippocampal ensembles and suggest that the hippocampal engram serves as an index of memory content.
Fos ensembles encode and shape stable spatial maps in the hippocampus
Authors: Noah L. Pettit, Ee-Lynn Yap, Michael E. Greenberg, and Christopher D. Harvey
Journal: Nature
Year: 2022
Group: Wongyo, Nicholas, and Anthony
Abstract: In the hippocampus, spatial maps are formed by place cells while contextual memories are thought to be encoded as engrams. Engrams are typically identifed by expression of the immediate early gene Fos, but little is known about the neural
activity patterns that drive, and are shaped by, Fos expression in behaving animals.
Thus, it is unclear whether Fos-expressing hippocampal neurons also encode spatial
maps and whether Fos expression correlates with and afects specifc features of the
place code. Here we measured the activity of CA1 neurons with calcium imaging
while monitoring Fos induction in mice performing a hippocampus-dependent
spatial learning task in virtual reality. We fnd that neurons with high Fos induction
form ensembles of cells with highly correlated activity, exhibit reliable place felds
that evenly tile the environment and have more stable tuning across days than nearby
non-Fos-induced cells. Comparing neighbouring cells with and without Fos function
using a sparse genetic loss-of-function approach, we fnd that neurons with disrupted
Fos function have less reliable activity, decreased spatial selectivity and lower
across-day stability. Our results demonstrate that Fos-induced cells contribute to
hippocampal place codes by encoding accurate, stable and spatially uniform maps
and that Fos itself has a causal role in shaping these place codes. Fos ensembles may
therefore link two key aspects of hippocampal function: engrams for contextual
memories and place codes that underlie cognitive maps.
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: Nicholas and Wongyo
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.
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: Nathaniel, Anthony, and Ange
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.
Mesolimbic dopamine adapts the rate of learning from action
Authors: Luke T. Coddington, Sarah E. Lindo, and Joshua T. Dudman