Driving fast-spiking cells induces gamma rhythm and controls

sensory responsesCardin et al., 2009

Rhythms of the BrainTuesday, November 30, 2010

Timothy Leonard

Background/Theory

The gamma cycle (Fries, Nikolic, & Singer, 2007)1. rhythmic network inhibition interacts with

excitatory input to pyramidal cells2. 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

Time

Level of Inhibition

Exci

tato

ry D

rive

+++++ + +++

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 EXChR2: bacteriorhodopsin Chlamydomonas reinhardtii channelrhodopsin-2 (FS-PV+: parvalbumin-positive fast-spikingChR2-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 were1. spontaneously occurring2. 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 light-evoked 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-spikingChR2-mCherry: AAV DIO ChR2-mCherry