Noradrenergic Control of Thalamic Oscillation: the Role of alpha-2 Receptors.
The effects of alpha-adrenergic drugs on neocortical high voltage spike and wave spindles (HVS), reflecting thalamic oscillation, was investigated in freely moving rats. HVS occurred spontaneously in the awake but immobile animal. Peripheral administration of the alpha-1 antagonist, prazosin and alpha-2 agonists, xylazine and clonidine increased the incidence and duration of HVS in a dose-dependent manner. The alpha-2 antagonist, yohimbine and the tricyclic antidepressants, desipramine and amitriptyline, significantly decreased the incidence of the neocortical HVS. Bilateral microinjections of the alpha-2 agonists into the nucleus ventralis lateralis area of the thalamus, but not into the hippocampus or corpus callosum, was as effective as peripheral injection of these drugs. Xylazine was most effective in Fischer 344 rats that display high spontaneous rate of HVS and less effective in the Sprague - Dawley and Buffalo strains. The HVS-promoting effect of clonidine was antagonized by prior intrathalamic injection of the alpha-2 antagonist, yohimbine. The amplitude of the HVS was increased by picomole amounts of unilaterally-injected clonidine. Neurotoxic destruction of the thalamopetal noradrenergic afferents by intracisternal or intrathalamic injection of 6-hydroxydopamine, but not by peripheral administration of DSP-4, increased the incidence of HVS. Importantly, intrathalamic administration of xylazine continued to induce HVS after destroying the thalamic noradrenergic terminals. Following downregulation of the alpha-2 adrenoceptors by chronic administration (3 weeks) of amitriptylene the incidence of HVS decreased and the effectiveness of intrathalamic xylazine on the induction of HVS was significantly reduced. Based on these findings, we suggest that a major action of alpha-2 adrenergic drugs on thalamic oscillation may be mediated by postsynaptic alpha-2 adrenoceptors located on the thalamocortical neurons. We hypothesize that noradrenaline in the thalamus has a dual effect on the relay cells: blocking and promoting thalamic oscillation via alpha-1 and alpha-2 receptors, respectively. The final physiological effect is assumed to be a function of the relative density and affinity of these adrenergic receptor subtypes.
Buzsáki
G.
G
Center for Molecular and Behavioral Neuroscience, Rutgers University, 195 University Avenue, Newark, NJ 07102, USA.
Kennedy
B.
B
Solt
V. B.
VB
Ziegler
M.
M