NEOCORTICAL CIRCUIT MECHANISMS OF SENSORIMOTOR PROCESSING
Sensorimotor processing is a dynamic process by which the central nervous system combines sensory inputs with motor commands to generate appropriate actions, a process underlying almost every aspect of normal behavior. In the somatosensory (touch) system, two major pathways carry sensory information from the periphery into the neocortex, with sensorimotor interactions happening at every level mediated by the motor cortex. Although much is known about sensorimotor interactions along the ascending sensory pathways, not much is known about sensorimotor interactions at the level of the neocortex. Using the mouse vibrissae (whisker) system, we aimed to understand the synaptic and cellular mechanisms governing sensorimotor interactions between the whisker representation of the primary somatosensory (vS1) and motor (vM1) cortices. Long-range interactions between cortical areas play a central role in cognitive function, but the dynamic regulation of these synapses (i.e., short-term synaptic plasticity) and their impact on a postsynaptic target neuron is unclear. In Chapter 2, we use optogenetic and electrophysiological strategies in vitro to study the long-range pathways connecting vM1 and vS1. We found that short-term synaptic facilitation was strong in both directions, as compared to other intracortical connections. This facilitation was dependent on the presynaptic calcium sensor synaptotagmin-7 and altered by several optogenetic approaches. Furthermore, the properties of the connections linking vS1 with secondary somatosensory cortex (vS2) resemble those from vS1 to vM1. These results reveal a synaptic mechanism by which intracortical projections may mediate specific changes in cellular excitability with repetitive activity. Moreover, previous literature has shown that vM1 can alter sensory processing in the ventral posteromedial nucleus (VPm) of the thalamus via the recruitment of corticothalamic (CT) neurons in layer 6 (L6) of vS1. Indeed, L6a CT neurons can modulate thalamic activity to shape sensory throughput into the cortex. However, direct influence of M1 on the two main classes of L6a CT cells in S1 has been understudied, likely due to technical challenges in their identification. Using retrograde tracing, in vitro recordings, and optogenetic control strategies in mice, we investigated the synaptic effects of vM1 input on the two main classes of L6a CT neurons. Our results reveal selective engagement by vM1 of CT neurons projecting to both the VPm and posteromedial (POm) nuclei in the thalamus (“Dual” CT neurons). These neurons exhibited spiking activity exclusively when held at a depolarized membrane potential simulating an “active state”. This selective engagement is possibly due to the differences in intrinsic membrane physiology making these Dual CT neurons more excitable, in addition to receiving stronger direct excitation from vM1. These findings provide new insights into the complex synaptic and circuit mechanisms underpinning neocortical sensorimotor interactions.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- In Copyright
- Material Type
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Theses
- Authors
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Martinetti, Luis Enrique
- Thesis Advisors
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Crandall, Shane R.
- Committee Members
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Leinninger, Gina
Cox, Charles L.
Vogt, Daniel
Wang, Hogbing
- Date Published
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2024
- Subjects
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Neurosciences
- Program of Study
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Neuroscience - Doctor of Philosophy
- Degree Level
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Doctoral
- Language
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English
- Pages
- 210 pages
- Permalink
- https://doi.org/doi:10.25335/21qt-8g89