Acute nigro-striatal blockade alters cortico-striatal encoding: an in vivo electrophysiological study

Abstract

Spreading of slow cortical rhythms into the basal ganglia (BG) is a relatively well-demonstrated phenomenon in the Parkinsonian state, both in humans and animals. Accordingly, striatal dopamine (DA) depletion, either acute or chronic, drives cortical-globus pallidus (GP) and cortical-substantia nigra pars reticulata (SNr) slow wave coherences in urethane-anesthetized rats. This paper investigates the striatal dynamics following acute DA depletion by tetrodotoxin (TTX) injection in the medial forebrain bundle (MFB) with respect to the transmission of slow cortical rhythms throughout the BG in more detail. The acute DA depletion offers the advantage of detecting electrophysiological changes irrespectively of chronically developing compensatory mechanisms. We observed that the acute blockade of the dopaminergic nigro-striatal pathway reshapes the firing rate and pattern of the different striatal neuron subtypes according to cortical activity, possibly reflecting a remodeled intrastriatal network. The observed alterations differ amongst striatal neuronal subtypes with the striatal medium spiny neurons and fast-spiking neurons being the most affected, while the tonically active neurons seem to be less affected. These acute changes might contribute to the diffusion of cortical activity to BG and the pathophysiology of Parkinson's disease (PD).

Keywords: Acute dopamine depletion; AutoCrl; BG; Basal ganglia synchronization; CV; Cortical local field potentials; DA; ECoG; FSI; ISI; MFB; MSN; PD; Parkinson's disease; SNc; SNr; STN; SWA; Striatum; TAN; TTX; autocorrelograms; basal ganglia; coefficient of variation; dopamine; electrocorticogram; fast-spiking interneuron; inter-spike interval; medial forebrain bundle; medium spiny neuron; nucleus subthalamicus; slow wave activity; substantia nigra pars compacta; substantia nigra pars reticulate; tetrodotoxin; tonically active large aspiny interneuron.