Optogenetic activation of nigral inhibitory inputs to motor thalamus in the mouse reveals classic inhibition with little potential for rebound activation

Jeremy R Edgerton,Dieter Jaeger

doi:10.3389/fncel.2014.00036

Abstract

The inhibitory output from the internal pallidum and substantia nigra to the thalamus forms an important link in the transmission of basal ganglia processing to cortex. Two hypotheses consider either inhibition of thalamic activity or thalamic excitation via post-inhibitory rebound burst firing as the functional mode of this link. We used optogenetics to characterize the synaptic properties of nigral input to motor thalamus in adult mouse brain slices, and to determine in what conditions the nigral inhibition of motor thalamus is transmitted via inhibition or rebound firing. Our results are more consistent with graded inhibition of spiking for conditions expected in normal awake animals, because inhibitory potentials from nigral input were generally not sufficient to elicit rebound spikes when the thalamic neurons were actively firing. However, with bursty or fast trains of nigral input low-threshold rebound spike bursts could be triggered for low levels of excitation. This may form the basis of pathological burst generation and transmission in parkinsonian conditions.

Highlights

The basal ganglia are thought to primarily exert their motor function in mammals by projecting to cerebral cortex via motor thalamus, the VA/VL thalamic nuclei in primates, and VM and rostroventral VA/VL in rodents (Sakai et al, 1998; Kuramoto et al, 2009, 2011)
A pause in the tonic basal ganglia output would lead to disinhibition of motor thalamus that results in the activation of movement or “action selection” (Gurney et al, 2001; Humphries et al, 2006)
This model of “classic” thalamic inhibition has recently been challenged by results showing that strong inhibitory inputs from the basal ganglia could result in rebound activation of thalamic neurons

Summary

Introduction

The basal ganglia are thought to primarily exert their motor function in mammals by projecting to cerebral cortex via motor thalamus, the VA/VL thalamic nuclei in primates, and VM and rostroventral VA/VL in rodents (Sakai et al, 1998; Kuramoto et al, 2009, 2011). A pause in the tonic basal ganglia output would lead to disinhibition of motor thalamus that results in the activation of movement or “action selection” (Gurney et al, 2001; Humphries et al, 2006) This model of “classic” thalamic inhibition has recently been challenged by results showing that strong inhibitory inputs from the basal ganglia could result in rebound activation of thalamic neurons. This possibility has been primarily supported by data from the basal ganglia output to the DLM thalamus in the songbird vocal learning circuit showing rebound activation after individual inhibitory inputs in brain slices (Person and Perkel, 2005) or anesthetized birds (Person and Perkel, 2007). This question is fundamental to our understanding of basal ganglia effects on cortical activity, and has been flagged as one of the most significant unknowns regarding basal ganglia function in prominent recent reviews of the field (Graybiel, 2005; Nambu, 2008)

Methods

Results

Conclusion