Dynamic corticothalamic modulation of the somatosensory thalamocortical circuit during wakefulness

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Abstract

The feedback projections from cortical layer 6 (L6CT) to sensory thalamus have long been implicated in playing a primary role in gating sensory signaling but remain poorly understood. To causally elucidate the full range of effects of these projections, we targeted silicon probe recordings to the whisker thalamocortical circuit of awake mice selectively expressing Channelrhodopsin-2 in L6CT neurons. Through optogenetic manipulation of L6CT neurons, multi-site electrophysiological recordings, and modeling of L6CT circuitry, we establish L6CT neurons as dynamic modulators of ongoing spiking in the ventro-posterior-medial nucleus of thalamus (VPm), either suppressing or enhancing VPm spiking depending on L6CT neurons’ firing rate and synchrony. Differential effects across the cortical excitatory and inhibitory sub-populations point to an overall influence of L6CT feedback on cortical excitability that could have profound implications for regulating sensory signaling across a range of ethologically relevant conditions.

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  1. exhibiting a monotonic relationship with LED intensity

    This is compelling and seems intuitive! Is there a way to determine whether changes in synchrony strength are based on increased firing rates of the same L6CT population or if you are activating greater numbers of L6CT cells as you increase LED intensity?

  2. This coupled with the strong activation of TRN at the lowest LED intensity likely contributes to the bidirectional influence of L6CT on VPm (see Discussion).

    This contribution to bidirectional influence is very interesting! Is there a way to experimentally test this hypothesis, perhaps with chemical or optogenetic inactivation of TRN while stimulating L6CT and recording from VPm?

  3. ramp-and-hold LED inputs

    I'm fascinated by the specific effects you see during ramp (e.g. suppression in Fig. 1e and 2e) as well as potential VPM ramping during hold in Fig. 2e and adaptation with stimulation in Fig. 2c with repeated trials. Do you think these effects are particular to the duration and intensity pattern of the stimulation in the same way you show other stimulation parameters (i.e. intensity and frequency content) dramatically change the effects of L6CT stimulation? Could you explain a little more about why you chose ramp-and-hold stimulation and the durations for your optogenetic stimulation?