Download Cellular mechanisms underlying network synchrony in the medial

Ch.2
Cellular mechanisms
underlying network synchrony
in the medial temporal lobe
Information Processing by Neuronal Populations
Edward O. Mann and Ole Paulsen
2008-12-17
Heo, Min-Oh
One-slide Summary

How does brain (especially Hippocampus) make
oscillation signals as constant frequency clock?
 Element level - from intrinsic cellular properties:
 Frequency
preference
 Self-sustained oscillation in a single neuron
 Structural level
 Recurrent
feedback loop
 Interaction between local network and global rhythm

So they can make theta-frequency, gamma-frequency,
delta-frequency and sharp wave – ripple complexes in
Hippocampus using mechanisms described above.
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Outline


1. Introduction
2. Basic cellular mechanisms contributing to cortical network
oscillations
 Intrinsic cellular properties : self-sustained oscillation
 Electrical synaptic coupling : Gap junction coupling
 Chemical synaptic coupling : combination of excitation and inhibition

3. Specific mechanisms underlying entorhinal and
hippocampal network oscillations






Slow oscillations
Gamma-frequency oscillations
Sharp wave-ripple complexes
Theta-frequency oscillations
4. Functional implications
5. Conclusion
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Rat hippocampal EEG and CA1 neural activity
- the theta (awake/behaving)
- LIA (slow-wave sleep)
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Introduction

Hippocampus
 Crucial role for Learning and consolidation of explicit memory
 plays major roles in short term memory and spatial navigation.
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The entorhinal cortex
 The entorhinal cortex (EC) forms the main input to the
hippocampus and is responsible for the pre-processing
(familiarity) of the input signals.
 On Medial surface, EC approximately maps to areas 28 and 34,
at lower left.
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Introduction

STDP (Spike Timing-Dependent Plasticity)
 Increasing or decreasing in the efficacy of synaptic
transmission (known as synaptic plasticity)
 The timing sensitivities are on the order of milliseconds.
 pre-post
spiking:
long-term potentiation (LTP)
 post-pre spiking:
long-term depression (LTD)
pre-post spiking by >40 ms
may also lead to LTD
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Brain Oscillation

STDP fails ?
 The inherent spike jitter affects converging inputs in
polysynaptic pathways
 The behaviorally relevant temporal associations

Oscillation in the cortical network
 Providing a mechanism to organize spike times
 Not yet resolved whether network oscillation serve temporal
association of behavior.
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Basic cellular mechanisms
contributing to cortical network oscillations

Hippocampal subfields follow a stereotypic
organizational principle
 Excitatory cells: ~80%
 Inhibitory cells: ~20%

Information Storing
 Mainly on the synaptic
connections between
excitatory neurons
 Cortical interneurons
control the precision
of spike timing
within cortical network
oscillations.
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Basic cellular mechanisms :
1. Intrinsic cellular properties
 A Neuron’s frequency preference
 Iin:
injecting sinusoidal input current
(linearly increasing freq. 0 to 100Hz)
 Vm: membrane potential
 Ih: hyperpolarization-activated
non-specific cation current
 INaP: persistent sodium current
 The neuron act as a band-pass filter.
 Sub- and suprathreshold oscillations
 There
may be a range of Vm in which
the neuron displays self-sustained
oscillation
 Rhythmic bursting
 The
inactivation and activation processes
of the low-threshold Ca2+ current can
mediate amplified resonance.
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Basic cellular mechanisms :
2. Electrical synaptic coupling

Ephaptic interactions
 Resulting from current flow in the extracellular space

Gap junction coupling
 Stronger and more reliable coupling than ephaptic interactions
 Bidirectional electrical connections preferentially
 Tend to act as low-pass filters
 Occur almost exclusively between interneurons belonging to the
same subtype.
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Basic cellular mechanisms :
3. Chemical synaptic coupling

Neuronal communication via neurotransmitter release
 Enables coupling over more distributed areas
 More diverse and dynamic

Coupling through excitatory synapses





Can act to synchronize intrinsic oscillators
Enable the emergence of rhythmic bursting
Positive feedback requires a mechanism to reduce activity
Not easy to explain the millisecond precision of spike timing
Synaptic inhibition
 Many interneurons coupled by mutual inhibition are capable of selfsynchronizing their output.
 Negative feedback loop can generate fast oscillations

Temporal control on time scales relevant for STDP
 Mediated through Inhibitory GABAergic transmission
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Specific mechanisms underlying entorhinal
and hippocampal network oscillations

Some stereotypical patterns of activity have provided the
basis for understanding some of the cellular mechanisms
underlying network synchrony.
 Theta-frequency
oscillations: Pacemaker
 Higher-frequency
oscillations:
Recurrent feedback loops,
Interneuronal network
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Specific mechanisms
underlying entorhinal and hippocampal network oscillations
:
1. Slow oscillations

States
 UP states: periods of sustained activity
 Down states: relative quiescence

Delta-frequency range ( < 4Hz )
 During slow-wave sleep (non-dreaming sleep)
 In the neocortex
 Rhythmic
bistable oscillation
 Intrinsically generated through recurrent synaptic excitation
 Hippocampal pyramidal neurons
 Not
display rhythmic bistability
 Influenced by propagated oscillations in the superficial layers of
the entorhinal cortex
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Specific mechanisms
underlying entorhinal and hippocampal network oscillations
:
2. Gamma-frequency oscillations (30-80Hz)
 In many sleeping and awake states
 Driven by two separate gamma generators in the superficial
layers of the entorhinal cortex and hippocampal CA3
respectively.
 Depends
on synaptic feedback loops
between pyramidal neurons and perisomatic-targeting interneurons
with the oscillation propagated via feedforward inhibition.
 Irrespective of the precise mechanism of generation, there fast
network oscillations could control principal cell spike timing
with a precision appropriate for STDP.
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Specific mechanisms
underlying entorhinal and hippocampal network oscillations
:
3. Sharp wave-ripple complexes

Sharp wave
 Randomly-timed large deflections of the EEG signal
lasting for 200-300 msec
 During slow-wave sleep and awake immobility
 Generated by recurrent excitation in the CA3
 Ripple oscillations (150-250Hz) ride on sharp waves in CA1
 The
frequency of ripple oscillations in vivo is sensitive to
benzodiazepines, which modulate the kinetics of GABAA–
receptor-mediated inhibition.
– On GABA-receptor-blocking situation, another cases are shown…
 Ripple-frequency
oscillations are associated with the rapid replay
of spike sequences previously observed during exploratory
behavior and could therefore enable information stored in the
hippocampus to be transferred to the neocortex.
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Specific mechanisms
underlying entorhinal and hippocampal network oscillations
:
4. Theta-frequency oscillations (4-12 Hz)
 The medium septum
 Lesions
of the medial septum - the central node of the theta system - cause
severe disruptions of memory.
 projects to all of the regions that show theta rhythmicity, and destruction of it
eliminates theta throughout the brain.
 During exploratory behavior and REM sleep
 The interaction between a local network oscillator and the global theta
activity offer the opportunity to control the local spike timing relative to that
of the external afferents at the millisecond timescale.
 The
spiking of principal neurons throughout hippocampus is phase-coupled
to the global theta rhythm.
 While global theta-frequency oscillations in vivo depend on subcortical
structures, individual cortical neurons, as well as the local networks, appear
tuned to participate in the theta-frequency rhythm.
 Subthreshold resonance in the theta-frequency range is observed in many
neuronal types.
 Phase precession: cells fire selectively in discrete regions of the animal’s
environment
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Functional implications
 STDP depends on
postsynaptic action potentials
 STDP mechanisms would be
activated maximally during
the replay of spike sequences
during sharp wave-ripple
complexes.
 Encoding interference problem
 Spike
time variability
represented phase precession or
spike sequences within gamma
cycles.
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Functional implications
 The reported phenomenon of phase precession
 cells with overlapping place fields along an animal’s
trajectory could fire at progressively earlier phases of the theta
oscillation.
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Conclusion

Network oscillations observed during different behaviors
clearly reflect which neuronal populations are active, and
how they communicate with each other.

It remains unclear whether this rhythmic coordination of
spiking activity has an independent functional role.

The intrinsic and synaptic properties of neurons seem
tuned to embrace network rhythmicity
© 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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