Driving fast-spiking cells induces
gamma rhythm and controls sensory
responses
Cardin et al., 2009
Rhythms of the Brain
Tuesday, November 30, 2010
Timothy Leonard
Background/Theory
The gamma cycle (Fries, Nikolic, & Singer, 2007)
1. rhythmic network inhibition interacts with
excitatory input to pyramidal cells
2. amplitude values converted into phase values
•
in the gamma cycle more excited cells fire earlier
3. Functional Consequences
•
enables fast processing and readout
–
–
‘winner take all’ algorithm
coincidence detection, rather than rate integration
1) The process is as follows:
• Big Picture: After excitatory input, the network of inhibitory
interneurons generates rhythmic synchronized activity and
imposes rhythmic inhibition onto the entire local network.
• Pyramidal cells will be able to respond
to excitatory input only during the
time window of fading inhibition.
• Pyramidal cells provide the major
excitatory drive to the interneurons
• interneurons discharge with some
phase delay relative to the
pyramidal cells
• resulting network inhibition
terminates the firing of both the
pyramidal cells and the
interneurons.
• The whole network is inhibited and the
next gamma cycle starts anew.
Taken from Fries, Nikolic, & Singer, 2007
^ area is important
for next slide
2) Conversion of excitatory drive into relative spike
timing
• If all pyramidal cells receive a similar amount of
phasic inhibition
– pyramidal cells receiving the strongest excitatory
drive will fire first during the phase of the cycle
Recoding Excitatory Drive into Relative Spike Timing
Excitatory Drive
Level of Inhibition
Time
+++++
+
+++
Early in phase, Inhibition at highest
Summary
1. rhythmic network inhibition interacts with
excitatory input to pyramidal cells
2. amplitude values converted into phase
values
– in the gamma cycle more excited cells fire
earlier
Investigating the Gamma Oscillation
with Optogenetics
• Cardin et al. 2009 – an overview
– Tested barrel cortex in mice in vivo
• processes information from the rodent whiskers
• Primary sensory area (S1)
• Detailed & orderly, equivalent to fingers on the hand – high acuity
– Light-driven activation of interneurons & pyramidal neurons.
• Electrophysiological recordings
– Relevant Findings
• Integral role of fast spiking interneurons in gamma oscillations
• Evidence of amplitude to spike timing recoding
Optogenetics Brief
• Light-sensitive ChR2
– activated by ~470 nm blue
light
• Interneurons
– targeted to FS-PV+
interneurons
• Fast Spiking
• Parvalbumin expressed only in
IN
• Excitatory neurons
– Targeted to αCamKII
• Expressed only in EX
ChR2: bacteriorhodopsin Chlamydomonas
reinhardtii channelrhodopsin-2 (
FS-PV+: parvalbumin-positive fast-spiking
ChR2-mCherry: AAV DIO ChR2-mCherry
Findings
Fast Spike activation generates gamma
oscillations
There should be a selective peak in LFP when
FS cells are driven in the gamma range.
– 20-80 Hz (optical stimulation) of FS cells
resulted in significant amplification of LFP
power in that same frequency band
– 8-24 (optical stimulation) Hz activation of
RS cells resulted in significant amplification
of LFP power in that same frequency band
– Gamma by FS - lower frequencies
by RS
• no effect on LFP power when
– FS cells at 8 Hz (optical stimulation)
– RS stimulation at 40 Hz (optical stimulation)
And LFP band
Natural gamma oscillations require FS activity
• Single light pulses during epochs of natural and evoked gamma Shifted the
phase of gamma oscillations that were
1.
2.
spontaneously occurring
evoked by midbrain reticular formation stimulation
– activation by the light pulse significantly increased the duration of the ongoing
gamma cycle
– Oscillations largely eliminated by blocking AMPA and NMDA receptors despite
high levels of evoked FS
FS stimulation during
naturally occurring gamma
• Increased duration of
the ongoing gamma
cycle
Evoked gamma phase regulates sensory processing
• Synaptic inputs arriving at
peak of inhibition
– Should have diminished
response
• Inputs arriving at the opposite
phase in gamma
– Should have large response.
To test :
• Stimulated FS cells at 40 Hz to
establish gamma
• recorded the responses of RS
cells to a single whisker
deflection
• Deflection presented at one of
five phases relative to a single
gamma cycle
• Timing of whisker-induced RS
action potentials relative to lightevoked inhibition and the gamma
cycle had a significant impact on
– Amplitude
– Timing
– precision of the sensory-evoked
responses of RS cells
Evoked gamma phase regulates sensory processing
• Gamma oscillations decreased the amplitude of
the RS sensory response at three phase points
– consistent with the enhanced level of overall
inhibition in this state
• Precision of sensory-evoked spikes was
significantly enhanced in a gamma-phase
dependent manner
Conclusions
• Data directly support the fast-spiking-gamma
hypothesis
• Provides the first causal evidence that distinct
network activity states can be induced in vivo by
cell-type-specific activation
– first causal demonstration of cortical oscillations
induced by cell-type-specific activation
• Demonstrates gated sensory processing in a
temporally specific manner
References
Cardin, J. A., Carlen, M., Meletis, K., Knoblich,
U., Zhang, F., Deisseroth, K., et al. (2009).
Driving fast-spiking cells induces gamma
rhythm and controls sensory responses.
Nature, 459(7247), 663-667.
Fries, P., Nikolic, D., & Singer, W. (2007). The
gamma cycle. Trends in Neurosciences, 30(7),
309-316.
Optogenetics More Detail
• Light-sensitive ChR2
– Cre-dependent expression of ChR2
• ChR2-mCherry
– activated by ~470 nm blue light
• Interneurons
– targeted to FS-PV+ interneurons
• Fast Spiking
• Parvalbumin expressed only in IN
– Injected into PV-Cre knock-in mice
– PV-Cre/FS mice
• Excitatory neurons
– Injected into αCamKII-Cre mice
– inducing recombination in excitatory
neurons
– αCamKII-Cre/RS mice
ChR2: bacteriorhodopsin Chlamydomonas
reinhardtii channelrhodopsin-2 (
FS-PV+: parvalbumin-positive fast-spiking
ChR2-mCherry: AAV DIO ChR2-mCherry