1. Rhythms and Cognition: Creation and Coordination of Cell Assemblies Nancy Kopell Center for BioDynamics Boston University

2. Rhythms and Cognition: Creation and Coordination of Cell Assemblies (Some) Neural Rhythms, Cell Assemblies And Some Hints That These Are Related To Cognition NK

3. Rhythms can be seen in EEG/MEG measurements Field recordings Single-cell recordings Measuring Rhythms Jensen et al. Bragin, et al. Whittington et al.

4. 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

5. General Mathematical Framework: Hodgkin-Huxley Equations Conductance x Electromotive force m and h satisfy

6. Inhibition Synchronizes Common inhibition: dv 1 /dt = I - v 1 - g syn e -t/  dv 2 /dt = I - v 2 - g syn e -t/  If  is “large”, equations have same “quasi-steady-state”. Initial conditions wash out; cells synchronize. Borgers, NK, White, Chow, Ritt, Ermentrout

7. 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

8. 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

9. 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.

10. 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”.

11. Persistent Gamma Rhythm and Vigilance Traub, 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

12. 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

13. The Consequences of Inattention

14. 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. AttentiveNot Attentive

15. Timing and Plasticity “Cells that fire together (?) wire together” Change of synapse strength depends on timing: AB 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

16. 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 AB

17. 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

18. 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.

19. A More Complicated Cell O-LM cell: a kind of “theta cell” C dv/dt = -  I ion Currents: spiking currents + I na,p + I h,s + I h, 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.

20. 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”

21. 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.