Heterogeneity of interneuron circuit function in sensory processing and synaptic plasticity
Thesis (Ph.D.)--Georgetown University, 2011.; Includes bibliographical references.; Text (Electronic thesis) in PDF format. Cortical GABAergic inhibitory interneurons are highly diverse in their morphologies, action potential firing patterns and biochemical markers. Fast spiking (FS) interneurons express parvalbumin, and low threshold spiking (LTS) interneurons express somatostatin as their biochemical markers. FS interneurons possess autaptic, synaptic, and electrical synapses that serve to mediate a fast, coordinated response in their postsynaptic targets and participate in numerous and diverse functions associated with cortical oscillations, sensory processing and developmental plasticity. Layer 4 FS interneurons can be strongly activated by thalamic afferents whereas the response of LTS interneurons to thalamic afferents is weak. LTS interneurons form electrical synapses and involve intracortical inhibitory transmissions.; In rodent barrel cortex, little is known about the contributions of individual cells and synapses in long-term sensory deprivation. We studied synaptic inhibition in four major types of neurons in layer 4 tangential slices. We discovered that long-term whisker deprivation selectively sped up the decay kinetics and increased the amplitude of the inhibitory postsynaptic currents (IPSCs) in LTS interneurons. Furthermore, through a combined pharmacologic and genetic approach, we identified the synaptic changes in LTS interneurons as an increase in alpha1-subunit mediated function. Because alpha1 subunits are commonly associated with circuit specific plasticity in sensory cortex, the switch in LTS interneuron synaptic inhibition may signal necessary circuit changes required for plastic adjustments in sensory-deprived cortex.; We examined the heterogeneity of FS interneurons in layer 4 barrel cortex using functional criteria previously employed to identify interneuron populations. We found that FS interneurons can be subclassified into two functional categories based on the onset of the first action potential at depolarization: Delayed Firing FS cells (FSD) and Early Onset Firing FS cells (FSE). Subtle variations in action potential firing patterns reveal 6 subtypes within these two categories. We discovered that FSD and FSE interneurons differ in intrinsic properties, inhibitory synaptic properties and in their responses to the evoked thalamic afferents. This study represents the first grouping of cortical FS interneurons into two distinct functional categories in layer 4 of the mouse barrel cortex.
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