The abrupt transition from theta to hyper-excitable spiking activity in stellate cells from layer II of the medial entorhinal cortex - PowerPoint PPT Presentation

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The abrupt transition from theta to hyper-excitable spiking activity in stellate cells from layer II of the medial entorhinal cortex

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Title: The abrupt transition from theta to hyper-excitable spiking activity in stellate cells from layer II of the medial entorhinal cortex


1
The abrupt transition from theta to
hyper-excitable spiking activity in stellate
cells from layer II of the medial entorhinal
cortex
  • Horacio G. Rotstein
  • Department of Mathematical Sciences
  • New Jersey Institute of Technology
  • Network Synchronization From dynamical systems
    to neuroscience
  • Leiden (NL) - May 27, 2008

2
Collaborators
  • Tilman Kispersky
  • Program in Neuroscience - Boston University
  • Nancy Kopell
  • Math Center for BioDynamics Boston
    University
  • Martin Wechselberger
  • Math University of Sidney
  • John White
  • Biomedical Engineering University of Utah

3
Entorhinal Cortex Hippocampus
  • Photomicrograph of a section through the rat
    hippocampal region (Gluck Myers). Adapted from
    Amaral Witter (1989).
  • Photomicrograph of a section through the
    rat hippocampal region (Gluck Myers). Adapted
    from Amaral Witter (1989)

4
Stellate cells (SCs)
  • Entorhinal cortex (EC) is the interface between
    the neocortex and the hippocampus.
  • Information flows from the neocortex
  • to the hippocampus through the
  • superficial layers (II and III) of the EC.
  • SCs are the most abundant cell type
  • in layer II of the EC.
  • SCs are putative grid cells.

5
Subthreshold oscillations (STOs)
  • SCs develop rhythmic STOs at theta frequencies (8
    12 Hz).
  • Spikes occur at the peaks of STOs but not at
    every cycle.
  • Interaction between two currents h- and
    persistent sodium.
  • Single cell phenomenon
  • Depolarization increases from 1 to 3 (Adapted
    from Dickson et al., J. Neurophysiol., 2000)

6
SCs Theta regime (background)
  • SCs have intrinsic biophysical properties that
    endow them with the ability to display rhythmic
    activity in the theta frequency regime (8 12
    Hz)
  • Subthreshold oscillations (STOs) interaction
    between a persistent sodium and a
    hyperpolarization-activated (h-) current.
  • Spikes
  • Mixed-mode oscillations (MMOs) STOs interspersed
    with spikes
  • R., Oppermann, White, Kopell (JCNS 2005)
  • R., Wechselberger, Kopell (Submitted)
  • Focus issue on MMOs (Chaos 2008)

7
SCs Hyperexcitable regime (this project)
  • SCs have intrinsic biophysical properties that
    endow them with the ability to display spiking
    activity in the gamma frequency regime (60
    Hz).
  • This time scale can be uncovered by phasic
    excitation.
  • The frequency regime depends on a combination of
    intrinsic and network properties.
  • Kispersky, White R. ,
    Work in Progress.

8
SC dynamic structure
  • Nonlinearities and multiple time-scales in the
    subthreshold regime
  • How are they created?
  • How do they depend on the intrinsic SC
    biophysical properties?
  • How do they interact with synaptic (excitatory
    and inhibitory) inputs?

9
SC biophysical model
10
SC biophysical model
11
SC biophysical model
12
Subthreshold oscillations (STOs) and spikes in
the SC model
13
STOs generated by persistent sodium channel
noise in the SC model
14
Subthreshold Regime Reduction of Dimensions
  • Multiscale analysis
  • Identification of the active and inactive
    currents
  • Identification of the appropriate time scales

15
Subthreshold Regime Reduction of Dimensions
  • Multiscale analysis
  • Identification of the active and inactive
    currents
  • Identification of the appropriate time scales

16
Subthreshold regime reduced SC model
SC biophysical model
Subthreshold regime
17
Subthreshold regime reduced SC model
18
Subthreshold regime reduced SC model
19
Subthreshold regime reduced SC model
SC biophysical model
Subthreshold regime
20
Subthreshold regime reduced SC model
21
Nonlinear Artificially Spiking (NAS) SC model
22
Nonlinear Artificially Spiking (NAS) SC model
23
Nonlinear Artificially Spiking (NAS) SC model
24
Inhibitory inputs can advance the next spike by
killing an STO.
25
Transition from theta to hyper-excitable (gamma)
rhythmic activity
  • Experimental (in vitro) results
  • There exist recurrent connections among SCs.
  • These connections are similar in normal
    (control) and epileptic cells.
  • Recurrent inhibitory circuits are reduced in
    epileptic cells as compared to normal (control)
    ones.
  • Recurrent circuits in layer II of MEC in a
    model of temporal lobe epilepsy. Kumar,
    Buckmaster, Huguenard, J. Neurosci. (2007)

26
Minimal S-I network model
27
Minimal S-I network model
  • A minimal S-S network reproduces the
    experimentally found transition form normal
    activity to hyper-excitability in SCs due to lack
    of inhibition

28
Minimal S-I network model
  • A minimal SIS network reproduces the
    experimentally found transition form normal
    activity to hyper-excitability in SCs due to lack
    of inhibition

29
Minimal SC network model (no inhibition)
  • A small increase in the SC recurrent synaptic
    conductance causes an explosion of the SC firing
    frequency

30
Minimal SC network model (no inhibition)
  • A small increase in the SC recurrent synaptic
    conductance causes an explosion of the SC firing
    frequency

31
Minimal S-I network model
  • A small increase in the inhibitory input to the
    SCs brings their frequency back to the theta
    regime

32
Single SC autapse (no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation
  • Single SC model representing a population of
    synchronized (in phase) SCs.

33
Single SC autapse (no inhibition)
  • Effects of changes in the maximal conductances

34
Single SC autapse (no inhibition)
  • Effects of changes in the maximal conductances

35
Single SC (no autapse - no inhibition)
36
Single SC (no autapse - no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

37
Single SC (no autapse - no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

38
Single SC (no autapse - no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

39
Single SC (no autapse - no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

40
Single SC (no autapse - no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

41
Single SC (no autapse - no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

42
Single SC (no autapse - no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

43
Single SC (no autapse - no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

44
Single SC autapse (no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

45
Single SC autapse (no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

46
Single SC autapse (no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

47
Single SC autapse (no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

48
Single SC autapse (no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

49
Single SC autapse (no inhibition)
  • The abrupt changes in the SC firing frequency are
    the result of phasic (synaptic) and not tonic
    excitation

50
Dynamic clamp experiments
  • Single SC autapse (no inhibition)
  • Tilman Kispersky John White

51
Dynamic clamp experiments
  • Voltage record of a stellate cell coupled to
    itself.
  • Inset close up view of a single burst
  • Under control conditions

52
Dynamic clamp experiments
  • Voltage record of a stellate cell coupled to
    itself.
  • Inset close up view of a single burst
  • Under linopiridine application (M-channel
    blocker)

53
Dynamic clamp experiments
  • Freq. vs. current under control conditions

54
Dynamic clamp experiments
55
Minimal S-I network model
56
Summary
  • SCs have intrinsic biophysical properties that
    endow them with the ability to display rhythmic
    activity in the theta and gamma frequency
    regimes (nonlinearities and time scale
    separation)
  • In normal conditions SCs display theta rhythmic
    activity (STOs and MMOs.
  • Abrupt transitions resulting from recurrent
    excitation.
  • Theoretical predictions confirmed by dynamic
    clamp experiments (Tilman Kispersky)
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