Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, C88
Differential control of striatal inhibition by histamine
T. Ellender1, I. Huerta-Ocampo1, M. Capogna1, P. Bolam1,2
1. MRC Anatomical Neuropharmacology Unit, University of Oxford, Oxford, United Kingdom. 2. Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
The striatum receives input from the histaminergic system arising in the hypothalamus. Histaminergic neurons exhibit a diurnal rhythm in their activity, being active during wakefulness and relatively silent during sleep. Consequently, the striatum is likely to experience a relatively high concentration of histamine during wakefulness. This, combined with the high expression of histamine receptors in the striatum, suggests that histamine might have a regulatory role in striatal function. We examined the effect of histamine on the main excitatory and inhibitory inputs to the principal neuron of the striatum, the GABAergic medium spiny projection neurons (MSNs). We performed whole-cell patch-clamp recordings of single MSNs, pairs of connected MSNs and pairs of connected interneurons and MSNs in acute slices of mice. We investigated the effect of bath-applied histamine (10 µM) in conjunction with selective histamine receptor antagonists on the excitatory responses evoked by cortical or thalamic stimulation or inhibitory responses evoked by local stimulation or unitary inhibitory responses between pairs of neurons. Both cortical and thalamic inputs to MSNs were negatively modulated by bath applied histamine, which was prevented by co-application of the H3 receptor antagonist, thioperamide (10 µM). Similarly, inhibitory inputs evoked by local stimulation were negatively modulated by bath applied histamine. However, in paired recordings we found that only the unitary inhibitory responses between pairs of MSNs were significantly reduced by histamine, whereas those between fast spiking (FS) interneurons and MSNs were unaffected. Histaminergic innervation of the striatum is thus involved in the negative regulation of both of the main excitatory inputs and the feed-back inhibitory input to MSNs, but does not affect the feed-forward inhibitory input from the FS interneurons. The selective attenuation of feed-back inhibition by histamine will alter the dendritic processing of excitatory inputs and thus the expression of basal ganglia function.
Where applicable, experiments conform with Society ethical requirements