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
Measuring Rhythms
Jensen et al.
Bragin, et al.
Rhythms can be seen in
• EEG/MEG measurements
• Field recordings
• Single-cell recordings
Whittington et al.
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.
General Mathematical Framework:
Hodgkin-Huxley Equations
dv
c
   I ion  D 2 v   I synapse
dt
I ion  g m j h ( v  VR )
Conductance x Electromotive force
m and h satisfy
dx
 ( x ( v )  x ) /  x
dt
Inhibition Synchronizes
Common inhibition:
Borgers, NK, White,
Chow, Ritt,
Ermentrout
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.
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 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.
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
The Consequences of Inattention
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.
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
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
Rhythms to the Rescue
Example: auditory cortex (Soto, Kamal, NK)
L1 Thalamocortical input
Frequency of the thalamic
input determines if
synapse gets stronger or
weaker.
Input:
Slower
Two different gamma rhythms:
• Input from L1 creates gamma in
E-I network
• Input to E-I from thalamus has
independent frequency
Faster
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
LM
O-
• Cell produces subthreshold oscillation at 4-8 Hz,
spiking oscillations at higher freq.
0.
10
I
-II
01
9.
.0
11
O-LM is inhibitory.
Whittington
• Frequencies come from kinetics of currents
(Alonso, Klink, White…)
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”
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