 |
 |
 |
 |
|
||||
 |
|
||||
|
|
Workshop 1 Abstracts and Lecture Materials:
Author: Steven
Baer, Arizona State University In human psychophysics, it is well known that after a brilliant
desensitizing flash, cone flicker sensitivity first increases but
then, paradoxically, decreases with a time course paralleling rod
dark adaptations. This interaction between rods and cones is called
suppressive rod-cone interaction (SRCI). Analogous physiological
effects involving rod and cone signals occur in horizontal cells
and bipolar cells. For example, in cat, dim backgrounds can enhance
small-spot flicker responses of retinal horizontal cells. This is
called background-induced flicker enhancement. We formulate a biophysically
based model to simulate background-induced flicker enhancement and
its spatial properties. In this model we assume that depolarized
horizontal-cell dendritic terminals, in a feedback effect, decrease
the entry of calcium into the cone terminal. Hyperpolarization of
the horizontal cell reduces this effect, allowing calcium to enter
the terminal, stimulating transmitter release by the cone presynaptic
apparatus. The result is an increase in synaptic gain. This accounts
for how peripheral rod-induced, horizontal-cell hyperpolarizations,
conducted centripetally to the horizontal-cell dendritic terminals
via gap junctions, can enhance postsynaptic cone responses. Background-induced
flicker enhancement also depends on the size of the test stimulus.
We explore this with a spatial model that includes the thousands
of horizontal cell processes (dendritic spines) entering cone pedicles.
The role of the synapse as the center of learning and memory in
neuronal systems is now widely appreciated. Synaptic plasticity
occurs in both presynaptic and postsynaptic regions of the synapse,
and takes place over a range of time scales. This plasticity can
be viewed as a means for filtering information in the form of electrical
signals. At the presynaptic terminal, synaptic depression and various
forms of facilitation due to plasticity in the transmitter release
mechanism are well-known sources of short-term plasticity. Another
form of plasticity has been the focus of a great deal of experimental
work over the past few years. This
Electrophysiological experiments have shown that activity-dependent synaptic modifications may depend on the precise timing of pre- and postsynaptic action potentials (spikes). Such spike timing-dependent plasticity (STDP) represents a quantitative extension of the Hebb's rule and has profound implications in the development and function of neuronal circuits. This talk will summarize experimental studies on STDP, including the description of spike-timing windows in cell culture and other systems, as well as the most recent development on the issue of STDP temporal integration.
Author: Amitabha
Bose, New Jersey Institute of Technology In many neuronal networks ranging in diversity from the crustacean
STG to the CA3 region of the hippocampus, neurons are capable of
maintaining phase relationships despite large changes in network
frequency. In this talk, we show how short-term synaptic depression
may act to promote phase maintenance.Using a simple model of an
oscillator coupled to a follower neuron by a depressing inhibitory
synapse, we show how the time to firing of the follower is a function
of synaptic strength. For a depressing synapse, synaptic strength
changes as a function of frequency. As a result, we obtain a network
in Author: Paul
Bressloff, University of Utah One of the major simplifying assumptions in many large-scale models
of cortical tissue is that the interactions between cell populations
are invariant under the action of the Euclidean group of rigid body
motions in the plane. Euclidean symmetry plays a key role in determining
the types of activity patterns and waves that can be generated in
these cortical networks. However, the assumptions of homogeneity
and isotropy are no longer valid when the detailed microstructure
of cortex is taken into account. In fact, cortex has a distinctly
crystalline-like structure at the mm length-scale, as exemplified
by the patchy nature of long-range horizontal (and feedback) connections
in primary visual cortex. These patchy connections are correlated
with a number of periodically repeating feature maps, in which local
populations of neurons respond preferentially to stimuli with particular
properties such as orientation, spatial frequency and left/right
eye (ocular) dominance. In this talk we present some recent analytical
results regarding the large-scale dynamics of cortex in the presence
of periodically modulated long-range interactions. Author: Nicolas
Brunel , Universite Paris How is the instantaneous firing rate modulated by inputs with sinusoidal
components at arbitrary frequencies in presence of realistic noise?
This question can been addressed analytically in several spiking
neuron models. The firing rate modulation of the leaky integrate-and-fire neuron
shows a resonant peak at the background firing rate of the neuron
that disappears at high noise, and the high frequency behavior is
shown to depend strongly on the correlation time constant of the
noise. The response decays at 1/sqrt(f) at high frequencies for
white noise, while it stays finite for colored noise. Author: Carson
Chow, University of Pittsburgh Experiments show that synapses can either increase their strength
(LTP), decrease their strength (LTD) or do nothing at all, depending
on the temporal relation between pre- and post-synaptic spiking
activity. It remains a puzzle as to how neurons are able to discriminate
spike-timing so precisely if at all. Here, I will first Author: Barry
Connors, Brown University Presentation Materials: PDF
PPT There are two types of synapses in the nervous system: chemical
synapses, which use diffusible extracellular molecules to transmit
signals between one cell and another, and electrical synapses, which
are comprised of intercytoplasmic channels that allow ionic current
to flow between cells. Chemical synapses are ubiquitous in the mammalian
brain. Electrical synapses had seemed to be quite rare, but new
molecular and physiological data suggest that electrical synapses
are far more widespread than suspected just a few years ago. Electrical
synapses now seem to be a major feature of the neural circuitry
in, among other things, the neocortex, hippocampus, thalamus, striatum,
cerebellum, retina, hypothalamus, brainstem, and spinal cord. I
will describe studies of electrical synapses between four distinct
sets of neurons in the neocortex, the thalamus, and the inferior
olive of the brainstem. The molecular and biophysical characteristics
of these four sets of electrical synapses are surprisingly similar.
Now that we appreciate their presence and properties, the greatest
challenge is to identify the functions of electrical synapses. I
will discuss some of the possibilities, namely that they serve to
coordinate the subthreshold and spiking activity of specific sets
of neurons, and that they play a role in the generation and synchrony
of neuronal rhythms. Author: Steve
Coombes, Loughborough University, UK Author: Bard
Ermentrout and Jan Karbowski, University of Pittsburgh Author: Marla
Feller, University of California at San Diego In the mammalian retina, highly correlated activity is present
weeks before vision in the form of spontaneous waves of action potentials
recorded from retinal ganglion cells. This activity is required
for the normal patterning of retinal ganglion cell axon arbors in
the developing thalamus. Recordings from retinal cells participating
in the waves demonstrate that wave generation requires synaptic
activation, indicating that the developing network consists of various
cell types connected through excitatory chemical synapses. Fluorescence
imaging has revealed that the propagating activity consists of spatially
restricted domains of activity that form a mosaic pattern over the
entire retina. The spatial properties of waves are not determined
by fixed structural units within the retina, rather they are determined
by the past history of wave activity. A biophysical model of the
network based on known anatomical and physiological properties of
the developing retina reproduces the same spatiotemporal properties
measured experimentally, and that these properties are determined
by a single variable which describes the local excitability of the
network. Consistent with this hypothesis, pharmacological manipulations
that alter local excitability also alter the spatiotemporal properties
of waves. This approach to describing the developing retina provides
unique insight into how the organization of a neural circuit can
lead to generation of complex, correlated activity patterns required
for the normal development of the nervous system. Author: David
Golomb, The Ohio State University Author: David
Hansel, Neurophysique et Physiologie du Système Moteur,
CNRS, Paris, France The existence of electrical synapses (ES) has been recently assessed in many regions of the mammalian brain. It has been also found that the spikes fired by interneurons interconnected with ES may get tightly synchronized. Here we investigate theoretically the conditions of emergence of synchronous activity in large networks of neurons coupled with ES. We consider two models. In the first one, which is analytically tractable, the neurons are fully connected and they are modeled with the "quadratic integrate-and-fire" dynamics which is a good approximation for the subthreshold behavior of a large class of neurons. The second model consists of randomly connected conductance-based neurons in which the voltage time course and the shapeof the linear response function of the neuron to small persturbations can be controlled by potassium currents and a persistent sodium current. We investigate analytically and numerically how the stability of the asynchronous state (AS) depends on the size of the action potentials fired by the neurons, on the after-hyperpolarization which follows it and on the duration of the refractory period. We predict that potassium currents promote synchrony mediated by ES whereas sodium currents oppose it. Author: Dan
Johnston, Baylor College of Medicine The dendrites of hippocampal CA1 pyramidal neurons receive inputs
from tens of thousands of excitatory and inhibitory synapses. The
dendrites must coordinate and blend these inputs to produce an output
in what is called synaptic integration. The dendrites also participate
in the dynamic adjustment of the synaptic strengths of these inputs
during synaptic plasticity. Dendrites were previously thought to
be mostly passive structures that provided some form of algebraic
summation of excitatory and inhibitory inputs. Using new techniques
of dendritic patch clamp recordings and fluorescence imaging, a
great deal of new information is now available concerning how dendrites
perform synaptic integration and participate in synaptic plasticity.
Using cell-attached patch recordings from dendrites of CA1 neurons,
we have mapped the distribution and characterized the properties
of voltage-gated Na+, Ca2+, and K+ channels along the apical dendrites.
We found that the density of Na+ channels is approximately the same
from the initial segment of the axon, through the soma, and up to
at least the first 350 µm of the apical dendrites. The total
density of voltage gated Ca2+ channels is also about the same from
the soma up to 350 µm from the soma. There are at least 5
di erent types of Ca2+ channels, however, and we found that these
were distributed di erentially along the soma-dendritic axis. For
example, the Land N-types are at a higher density in the soma and
proximal dendrites while the R- and T-types are at a higher density
in the distal dendrites. We also studied dendritic K+ channels.
We found that there is a fast, transient, A-type K+ channel in the
dendrites. Surprisingly, the density of this channel increases dramatically
with distance from the soma so that its density at 350 µm
is about 5-fold higher than that in the soma. This channel activates
rapidly and limits the amplitude of back-propagating, dendritic
action potentials as well as synaptic potentials. Recently, we found
that this K+ channel is modulated by several protein kinases. PKA
and PKC both shift the voltage range of activation of the channel
to more positive potentials thereby reducing the activity of these
K+ channels at any given membrane potential and increasing the amplitude
of synaptic potentials and back-propagating action potentials. The
actions of both of these kinases appears to be upstream of MAPK.
We also found that the K+ channels can be inactivated by brief trains
of synaptic input. Synaptic input can thus produce an increase in
the amplitude of back-propagating action potentials on the specific
branch receiving the input. If the synaptic input is appropriately
timed with the dendritic action potential, long-term potentiation
is induced. We thus hypothesize that these K+ channels play a role
in spike-timing dependent LTP. Furthermore, we have found local
increases in excitability following the induction of LTP, which
may be partly responsible for the phenomenon of E-S potentiation,
and we hypothesize that this increase in excitability is due to
local decreases in K+ channel activity. In conclusion, dendrites
are not passive structures, but contain a vast array of voltage-gated
ion channels. These channels play important roles in synaptic integration
and both the induction and expression of various forms of synaptic
plasticity. Author: David
Kleinfeld, Univeristy of California at San Diego The sensory system of animals is of limited value without the participation
of the elaborate motor apparatus that moves the sensors into useful
positions. I will focus on behavioral and computational aspects
of the vibrissa somatosensory system in rat, and review the experimental
evidence for phase-sensitive detection as a model for discriminating
contact with an object and as a means to control the position of
the vibrissae. A theme of the talk is that principles from communication
and control engineering provide a framework to guide experiments. Author: Nancy Kopell,
Boston University Author: Tim
Lewis, New York University Author: Henry
Markram, Weizmann Institute of Science
Author: David
McLaughlin , New York University Author: Fazan
Nadim, Rutgers University When depressing synapses are embedded in a circuit composed of a pacemaker neuron and a neuron with no autorhythmic properties, the network can show two modes of oscillation. In one mode the synapses are mostly depressed and the oscillations are dominated by the properties of the oscillating neuron. In the other mode, the synapses recover from depression and the oscillations are largely controlled by the synapses. We demonstrate the two modes of oscillation in a hybrid circuit consisting of a biological pacemaker and a model neuron, reciprocally coupled via model depressing synapses. We show that across a wide range of parameter values this network shows robust bistability of the oscillation mode, and that it is possible to switch the network from one mode to the other by injection of a brief current pulse in either neuron. The underlying mechanism for bistability may be present in many types of circuits with reciprocal connections and synaptic depression.
Author: Duane
Nykamp, University of California at Los Angeles Author: David Pinto,
Brown University Author: John
Rinzel, Center for Neural Science and Courant Institute of Mathematical
Sciences, 1. Tabak, J., Senn, W., O'Donovan, M.J., & Rinzel, J. (2000). Modeling of spontaneous activity in developing spinal cord using activity-dependent depression in an excitatory network. J. Neuroscience, 20, 3041-3056. 2. Tabak, J., Rinzel, J., & O'Donovan, M. (2001). The role
of activity-dependent network depression in the expression and self-regulation
of spontaneous activity in the developing spinal cord. J. Neuroscience,
21, 8966-8976. Author: Jonathan
Rubin, University of Pittsburgh Author: Michael
Rudolph, UNIC-CNRS Author: Robert
Shapley, Center for Neural Science NYU Author:
Michael Shelley, New York University Author: Arthur
Sherman, N.I.H.
Experimental and modeling studies of the neural oscillator generating the rhythm of breathing in the mammalian brainstem are providing insights into cellular and network-level mechanisms generating rhythms in motor pattern generation networks. We have developed a hybrid pacemaker-network model of the respiratory oscillator that represents a synthesis of cellular and network mechanisms derived from experimental and modeling studies. This model incorporates a rhythm-generating neuronal kernel, located in the pre-Bötzinger complex of the ventrolateral medulla, consisting of a network of excitatory neurons with state (voltage)-dependent, oscillatory bursting/pacemaker-like properties. This kernel has been experimentally isolated in several in vitro preparations from neonatal rodents including thin brainstem slices with a functionally intact, active rhythm-generating network. We have exploited these in vitro systems for analysis of cellular biophysical mechanisms and population-level dynamics in the kernel by a combination of single-cell patch-clamp electrophysiological recording, activity-dependent neuron/population imaging and recording of population activity. Simulations with mathematical models of the pacemaker cell network are consistent with a number of features of measured cell and population rhythmic behavior that will be discussed in the talk, including the following. (1) Cellular biophysical mechanisms of oscillatory burst generation. Electrophysiological studies show that candidate rhythm-generating cells exhibit intrinsic voltage-dependent bursting behavior with burst frequencies spanning over an order of magnitude (.05 to ~1Hz), providing a mechanism for cellular-level frequency control. This behavior is mimicked by our biophysically minimal models incorporating Hodgkin-Huxley-like membrane conductances, where bursting arises via fast activation-slow inactivation of a subthreshold voltage-activating persistent sodium current (INaP) that dynamically interacts with a potassium-dominated leak current. Our voltage-clamp measurements have demonstrated INaP in bursting cells and dynamic clamp studies incorporating our modeled INaP in neurons confirm that this mechanism is sufficient for voltage-dependent oscillatory burst generation. (2) Synaptic coupling and burst synchronization. Electrophysiological and imaging studies indicate that cellular burst synchronization in the kernel arises from fast, glutamatergic excitatory synaptic coupling. Modeling studies of heterogeneous populations of synaptically-coupled bursting neurons (as described above) indicate that burst synchronization across the population is promoted by burst-generating currents and can occur to produce stable rhythms even when only a small fraction of the cells in the population are intrinsically bursting. Population bursting frequency is modulated by synaptic coupling strength. (3) Cellular/population frequency control and dynamic range. Experimentally tonic excitation regulates single cell and population bursting frequency; population bursting exhibits a wider dynamic range of frequency control by tonic excitation. Population model simulations mimic this and indicate that heterogeneity of cellular bursting parameters and excitatory coupling synergistically combine to determine dynamic range. (4) Multiple oscillatory modes and quasiperiodic dynamics. Measurements of population activity combined with nonlinear system dynamics analysis indicate that the kernel intrinsically exhibits multiple periodic states as frequency is driven experimentally by tonic excitation. Stable periodic behavior occurs with low excitation, progresses to mixed mode-oscillations, and transitions to quasiperiodic behavior at high excitation levels. Population simulations indicate that weak synaptic coupling and extreme parameter heterogeneity, leading to partial desychronization of cellular bursting, can give rise to mixed mode oscillations and quasiperiodic states. References. 1. Butera, R.J., Rinzel, J. & Smith, J.C. (1999). Models of
respiratory rhythm generation in the pre-Bötzinger complex.
I. Bursting pacemaker neurons. J. Neurophysiology, 81, 382-397. Author: David
Terman, Mathematical Biosciences Institute - The Ohio State
University
A major outstanding problem in sensory physiology
is to understand how the response of a retinal rod to a single photon
manages to have such little variation in amplitude and kinetics,
despite the fact that it is mediated by the activity of a single
molecule of activated rhodopsin (R*). In the dark, there is a circulating
current across the rod membrane, which flows inward through channels
in the outer segment membrane gated by cyclic-GMP, and flows outward
across the inner segment membrane. The modulation of the voltage
across the rod membrane in response to light is a consequence of
the reduction of this dark (light-sensitive) current by the following
mechanism. When rhodopsin absorbs a photon it is converted into
an activated enzyme (R*) that initiates a cascade of biochemical
reactions: G-protein is activated by R*; G-protein activates phosphodiesterase;
phosphodiesterase hydrolyzes cyclic-GMP; the cyclic-GMP concentration
drops, resulting in closure of some of the light-sensitive channels;
the reduction of inward current causes the rod membrane voltage
to become hyperpolarized. The sequence of events following the activation
of rhodopsin continues until R* is inactivated. The regularity of
the single-photon response implies that the lifetime of R* is controlled
with high precision. Numerous theories have been proposed. All are
based in part on known biochemical elements of the transduction
cascade, and some also include additional hypothetical mechanism.
Liebman and Gibson recently proposed a theory based on their biochemical
experiments. The idea is that R* is partially deactivated by multiple
steps of phosphorylation catalyzed by rhodopsin kinase, followed
by an irreversible "capping" reaction in which R* is completely
inactivated by arrestin. In this theory, three molecules, rhodopsin
kinase, G-protein and arrestin, compete in a mutually exclusive
manner for R*. Every time R* is phosphorylated, its affinity for
G-protein (i.e. its catalytic activity) is reduced, its affinity
for rhodopsin kinase is reduced, and its affinity for arrestin is
increased. I will explain how some statistics of the single-photon
responses can be derived analytically in this theory. I will also
demonstrate by Monte Carlo simulation the extent to which the proposed
mechanism reduces variability in the single-photon response. Deficiencies
of the theory will be demonstrated, and alternative mechanisms will
be discussed and evaluated. Author: Roger
Traub, State University of New York "In 1998, it was hypothesized that gap junctions existed between
the axons of hippocampal pyramidal cells. This hypothesis was suggested
by two experimental observations: the occurrence of 200 Hz population
oscillations in neuronal networks in which synaptic transmission
was blocked, but where the oscillations required gap junctions;
and the shape of putative coupling potentials in principal neurons,
which were too fast to be generated by gap junctions located on
somata or dendrites. There is now electrophysiological and dye-coupling
evidence that such gap junctions exist, and are located roughly
100 microns from the soma. Modeling shows that gap junctions in
this location can give rise to very fast oscillations in networks
of principal neurons, as well as to 200 Hz "ripples" (as
seen in vivo, and consisting of IPSPs), when interneurons are also
in the circuit. In addition, axonal gap junctions can underlie the
generation of 40 Hz oscillations, in the presence of cholinergic
agonists or of kainate. Modeling predicts, and experiments confirm,
that in such conditions, the oscillation spectrum contains both
40 Hz and also very fast (>80 Hz) components." Author: Philip
Ulinski, University of Chicago Visual stimuli evoke waves of activity that propagate throughout
the visual cortex of freshwater turtles. These waves have been visualized
using both multielectrode recording and voltage sensitive dye methods.
This talk will discuss the use of a large-scale model of turtle
visual cortex to study the cellular mechanisms underlying the propagation
of the wave and to suggest that information about visual stimuli
is encoded in the temporal dynamics of the waves. Author: Carl
Van Vreeswijk, Neurophysics and Physiology of the Motor Sys.
Over the last ten years we have gained significant insight in the role of synaptic interactions in the synchronization of neuronal networks. A crucial first in these investigations was the study of extremely simplified networks, all-to-all coupled networks of indentical neurons. The mathematical tools developed to analyse both the asynchronous and fully synchronized state in such networks were subsequently extended to study networks with more realistic architectures. However, long term behavior in spatially extended networks of synaptically coupled neurons, in which the coupling strength decreases with distance, have not yet received much attention. In this talk I will consider a network of identical integrate-and-fire neurons, positioned on a 1-D ring. I will show that strongly coupled networks of oscil- lators behave qualitatively differently from weakly coupled ones, and also differ qualitatively from rate based models. Such networks can evolve, depending on the coupling parameters, evolve to either an asynchronous state, or to a traveling wave state. I will show how the existence and stability of these states can be analyzed in this simple model. For fast excitatory synapses a third state co-exist with the travelling wave state. In this state the activity is highly complex and the symmetry is broken. So far, no analytical treatment of this state has been found for this state. Author: Hugh
Wilson, York University
|
|
|||
