1. Ch.2 Cellular mechanisms underlying network synchrony in the medial temporal lobe
Information Processing by Neuronal Populations
Edward O. Mann and Ole Paulsen
Heo, Min-Oh

2. © 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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.
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3. © 2008, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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
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4. Rat hippocampal EEG and CA1 neural activity
- the theta (awake/behaving)
- LIA (slow-wave sleep)

5. 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.
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7. 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.
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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.
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10. 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.
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11. 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.
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12. 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 self-synchronizing their output.
Negative feedback loop can generate fast oscillations
Temporal control on time scales relevant for STDP
Mediated through Inhibitory GABAergic transmission
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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
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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
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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.
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16. 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 msec
During slow-wave sleep and awake immobility
Generated by recurrent excitation in the CA3
Ripple oscillations ( Hz) 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
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18. 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.
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19. 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.
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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
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