Activity-Dependent Regulation of Inhibition from Different Inhibitory Subtypes

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Title: Activity-Dependent Regulation of Inhibition from Different Inhibitory Subtypes
Author: Bartley, Aundrea Frances
Abstract: Neuronal activity , in the form of action potential firing , is critical in the maturation and maintenance of neocortical circuitry . A negative feedback mechanism by which neuronal circuits adapt to changing levels of average activity on a time scale of hours to days is known as homeostatic plasticity . At the simplest level , homeostatic adaptations occur to maintain firing rate of neurons at a particular set -point . To better understand homeostatic plasticity at the network level , one must understand the activity -dependent adaptations that occur in the different neocortical cells types . To this end , I examined the regulation of inhibitory neurons and their synapses . I used chronic pharmacological block of activity in a neocortical slice cultures to examine the role activity plays in regulating feedback inhibition defined by two biochemical inhibitory neuron subtypes - parvalbumin -positive (Parv+ ) and somatostatin -positive (Som+ ) . The cellular and synaptic components of local feedback inhibition were examined . I found that chronic activity blockade caused the following : 1 ) an increase in the intrinsic excitability of Som+ neurons through the downregulation of 2 substhreshold currents . While not thoroughly examined in Parv+ neurons , a similar , but weaker , increase in excitability may occur in these neurons as well . These < changes are consistent with a homeostatic maintenance of firing rate in these neurons . 2 ) a differential regulation of monosynaptic inhibition based on subtype that was frequency dependent . At low frequency action potential firing , Parv+ mediated inhibitory drive was downregulated while Som+ was unchanged . Both subtypes were likely downregulated at high frequency firing . 3 ) an upregulation of excitatory drive onto both Parv+ and Som+ neurons . This was most dramatic at low frequency firing where both subtypes displayed an almost 3 -fold increase . This is also consistent with homeostatic maintenance of firing rate in inhibitory neurons . 4 ) based on the above , a clear change in recurrent inhibition occurred at low frequency firing . First , net recurrent inhibition was increased for both subtypes , but the relative influence of the two changed , such that Som+ recurrent inhibition contributed more relative to that of Parv+ circuitry . At high frequency firing , a slight , but less resolvable , increase in net recurrent inhibition may have occurred in both subtypes without any change in relative contribution . 5 ) all of the synaptic changes were likely due to increases in presynaptic release probability and /or decreases in synapse number .
URI: http : / /hdl .handle .net /2152 .5 /690
Date: 2007-08-08


Activity-Dependent Regulation of Inhibition from Different Inhibitory Subtypes. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /690 .

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