Abstract TMP34: Longitudinal Calcium Imaging Reveals Circuit Switching and Abnormal Response Fidelity in Somatosensory Vip Interneuron Circuits in the Stroke Damaged Brain

Abstract

Although inhibitory cortical interneurons play a critical role in regulating brain excitability and function, the effects of stroke on these neurons is poorly understood. In particular, interneurons expressing vasoactive intestinal peptide (VIP) specialize in inhibiting other classes of inhibitory neurons, and thus serve to modulate cortical sensory processing. To understand how stroke affects this circuit, we imaged VIP neuron structure and function (using GCaMP6s) before and after focal stroke in forelimb somatosensory cortex. Stroke led to a significant loss of peri-infarct pre-synaptic boutons and dendritic spines that was followed by a wave of bouton/spine production. Larger-scale changes, such as pruning/growth of axons or dendritic branches was observed, albeit on a limited scale. Functionally, the fraction of forelimb responsive VIP interneurons and their response fidelity (defined as the % of forelimb responsive trials) was significantly reduced in the first week after stroke. The loss of responsiveness was most evident in highly active VIP neurons (defined by their level of responsiveness before stroke), whereas less active neurons were minimally affected. Of note, a small fraction of VIP neurons that were minimally active before stroke, became responsive afterwards suggesting that stroke may unmask sensory responses in some neurons. Although VIP responses to forepaw stimulation generally improved although not fully from 2-5 weeks recovery, the variance in response fidelity after stroke was comparatively high and therefore less predictable than that observed before stroke. Lastly, stroke related changes to synaptic structure and response properties were both restricted to within 400μm of the infarct border. These findings reveal the dynamic and resilient nature of VIP neurons and suggest that a sub-population of these cells are more apt to lose sensory responsiveness during the initial phase of stroke, whereas some minimally responsive cells are progressively recruited into the forelimb sensory circuit. Furthermore, stroke appears to disrupt the predictability of sensory evoked responses in these cortical interneurons which could have important consequences for sensory perception.