Date of Completion

Spring 5-1-2016

Thesis Advisor(s)

Joseph LoTurco

Honors Major

Physiology and Neurobiology

Disciplines

Anatomy | Biology | Developmental Biology | Neuroscience and Neurobiology | Physiology

Abstract

Cortical networks depend upon inhibition through the neurotransmitter GABA to control and coordinate specific spatiotemporal circuit patterns, underlying the exquisite complexity of neural signaling. Disinhibition, a form of inhibition where inhibitory neurons inhibit other inhibitory cells, further aids in amplifying local neural processing in a selective, organized manner. A subset of GABAergic interneurons, vasoactive intestinal peptide-expressing (VIP) cells, preferentially inhibit somatostatin interneurons, which provide inhibitory input onto pyramidal cells, thus creating an archetypal circuit illustrating disinhibition in the cortex. The aim of this anatomical study was to investigate variations in GABAergic VIP synapses onto somatostatin-expressing inhibitory interneurons in mice at different developmental stages. Through a series of age-based and regional quantifications of somatic terminals and terminal distances, we sought to determine the inception of these associations and their distances from the nuclei. Our data show that although VIP terminal distances remained within a similar range as the animal developed, there was a significant change in the number of VIP terminal associations onto SST cells. Pups at the age of one week had far fewer terminals than older juvenile or adult mice. Among brain regions, neocortical cells had a greater number of terminals than entorhinal cells, but terminal distances generally overlapped in range. The results support previous research about the critical period of VIP interneuron genesis, while regional diversity in terminals may highlight how this crucial disinhibitory circuit functions differently in the neocortex and entorhinal cortex. These findings have broad implications for understanding the temporal patterns of inhibitory circuit development, which can act as an important indicator of the differences between control animals and those expressing pathological conditions associated with dysfunctional inhibitory networks.

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