Rhythms and Cognition: Creation and Coordination of Cell Assemblies

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

4. Cell Assemblies and Function • 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.

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

6. Inhibition Synchronizes Borgers, NK, White, Chow, Ritt, Ermentrout Common inhibition: dv1/dt = I - v1 - gsyn e-t/t dv2/dt = I - v2 -gsyn e-t/t Iftis “large”, equations have same “quasi-steady-state”. Initial conditions wash out; cells synchronize.

7. Pyramidal -Interneuron Gamma (PING) • Whittington et al., J. Physiol. 1997 • PING is coherent withheterogeneity, 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 Attentive Not attentive • Removing ACh changes ionic currents. • (adds “M-current”) • Inhibition is now desynchronized. • Spread out inhibition suppresses the E-cells.

12. Gamma rhythms facilitate detection Attentive • “Lion cells” get input • Cell assembly forms (in PING) • Inhibition created by assembly suppresses other E-cells. 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 Not Attentive • 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.

15. 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 Bi and Poo 1998 • “Causal” order creates strengthening • What causes weakening?

16. Forced Oscillators and Timing A B • 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

17. Rhythms to the Rescue Example: auditory cortex (Soto, Kamal, NK) Frequency of the thalamic input determines if synapse gets stronger or weaker. L1 Thalamocortical input Input: Slower Faster • Two different gamma rhythms: • Input from L1 creates gamma in E-I network • Input to E-I from thalamus has independent frequency

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 patternedinput 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 = -  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.

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. 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. • Rhythms • Foster creation and coordination of cell assemblies, • Affect plasticity • Affect gating and response to inputs • Create an opportunity to marry mechanism and function