Rhythms and Cognition:

Creation and Coordination of Cell Assemblies

Nancy Kopell

Center for BioDynamics

Boston University

Rhythms and Cognition:

Creation and Coordination of Cell Assemblies

(Some) Neural Rhythms, Cell Assemblies

And Some Hints That These Are Related

To Cognition

NK

Rhythms can be seen in • EEG/MEG measurements• Field recordings • Single-cell recordings

Measuring Rhythms

Jensen et al. Bragin, et al.

Whittington et al.

Working hypotheses:

• Cell assemblies are important to function

• (Possible) uses: potentiating signals, plasticity (Hebb), gating

signals.

• Rhythms are associated with cell assemblies

• Gamma rhythms (30-80 Hz) are related to “binding”, early sensory processing, attention, awareness …

(Singer, Gray, Fries, Tallon-Baudry …..)

• Biophysical mechanisms for rhythms matters to formation, coordination and use of cell assemblies.

Cell Assemblies and Function

General Mathematical Framework:

Hodgkin-Huxley Equations

)(

2

Rj

ion

synapseion

VvhmgI

IvDIdt

dvc

Conductance x Electromotive force

m and h satisfy

xxvxdtdx /))((

Inhibition Synchronizes

Common inhibition:

dv1/dt = I - v1 - gsyn e-t/

dv2/dt = I - v2 - gsyn e-t/

If is “large”, equations have same “quasi-steady-state”.

Initial conditions wash out; cells synchronize.

Borgers, NK, White, Chow, Ritt, Ermentrout

Pyramidal -Interneuron Gamma (PING)

Whittington et al., J. Physiol. 1997

• PING is coherent with heterogeneity, sparse coupling (Borgers, NK)

• E-cells are synchronized by I cells, I cells are synch’d by E-cells

• Synchrony of both pops. depend on number of inputs to each cell

Persistent (Vigilance) Gamma Rhythm

Traub, Whittington, Borgers, Epstein, NK

• Can be induced in slices with acetylcholine (ACh)

• ACh is associated with attention

• Lasts a long time

• E cells each fire infrequently

• Population displays gamma rhythm

What Makes Gamma So Good (for Binding)

Olufsen and NK

• Gamma formed from simple currents; no memory from cycle to cycle

• Sparse gamma, other rhythms, use currents that last longer than gamma cycle, create memory.

Gamma and Attention

• Power in gamma frequency range increases when subject pays attention.

• Question: is gamma important for function?

• Claim:

• Gamma rhythm helps to detect small signals

• Gamma rhythm helps to foster detection of signals in the presence of

“distractors”.

Persistent Gamma Rhythm and VigilanceTraub, Whittington, Borgers, Epstein, NK

• Removing ACh changes ionic currents.

• (adds “M-current”)

• Inhibition is now desynchronized.

• Spread out inhibition suppresses the E-cells.

Attentive Not attentive

Gamma rhythms facilitate detection

• “Lion cells” get input

• Cell assembly forms (in PING)

• Inhibition created by assembly suppresses other E-cells.

Attentive

Not attentive

• Add M-current in simulation to slow down E-cells; rhythm disappears.

• “Lion cells” get same input as above

• Cells do not respond as well

• Lion is not noticed

The Consequences of Inattention

Gamma Rhythms Help Suppress “Distractors”

Attentive:

• Input to “dachshund cells” creates cell assembly.

• Slightly larger input to “lion cells” suppresses dachshund cells.

Not attentive:

• Cell assemblies are much weaker

• Lion does not suppress dachshund.

Attentive Not Attentive

Timing and Plasticity

• “Cells that fire together (?) wire together”

• Change of synapse strength depends on timing:

A B

If A fires before B, connection strengthens

If A fires after B, connection weakens

• “Causal” order creates strengthening

• What causes weakening?

Bi and Poo 1998

Forced Oscillators and Timing

If A and B are oscillators, and A “forces” B,

the relative timing of A and B depends

• Frequencies of A and B

• Nature of the signal from A to B

A B

Rhythms to the Rescue

Example: auditory cortex (Soto, Kamal, NK)

Two different gamma rhythms:

• Input from L1 creates gamma in E-I network

• Input to E-I from thalamus has independent frequency

Input:

Slower Faster

Frequency of the thalamic input determines if synapse gets stronger or weaker.

L1 Thalamocortical input

What Are The Roles of the Theta Rhythm?

• Hypothesis: Theta rhythms coordinate cell assemblies over space and time.

• Program: Understand how.

• Method:

• Understand natural dynamics (no input)

• Investigate effects of spatially and temporally patterned input to different structures (e.g., EC, CA3, CA1)

• Use as clues to coordination.

A More Complicated Cell

O-LM cell: a kind of “theta cell”

C dv/dt = - Iion

Currents: spiking currents + Ina,p + Ih,s + Ih, f

O-LM is inhibitory.

• Cell produces subthreshold oscillation at 4-8 Hz, spiking oscillations at higher freq.

• Frequencies come from kinetics of currents (Alonso, Klink, White…)

Whittington

Similar cells: spiny stellate cells of entorhinal cortex.

Rhythm(s) In CA3 In Vitro Depend on Slice Angle

Gloveli, Whittington, Rotstein, NK, …

• Transverse: gamma (30 Hz)

• Longitudinal: theta (6 Hz)

• Coronal: both

Relevant anatomy:

• O-LM cells project more in longitudinal direction

• Pyramidal cells project more in transverse direction

Model: “minimal”

Rhythms

• Foster creation and coordination of cell assemblies,

• Affect plasticity

• Affect gating and response to inputs

• Create an opportunity to marry mechanism and function

Where Do Rhythms Come From and What Are They Good For?

• Rhythms come from interactions of intrinsic and synaptic currents

• Can get same frequency from multiple mechanisms.