Journal of Alzheimers Disease & Parkinsonism
Open Access

Abstract

Hyperpolarization-activated Cyclicnucleotide-gated (HCN) channels occupy a critical position in globus pallidus pacemaking
activity. Morphological studies have shown the expression of HCN channels in the globus pallidus. To investigate
the in vivo effects of HCN channels in the globus pallidus, extracellular recordings and behavioral tests were performed in
the present study. In normal rats, micro-pressure ejection of 0.05 mM ZD7288, the selective HCN channel blocker, decreased
the frequency of spontaneous firing in 21 out of the 40 pallidal neurons. The average decrease was 50.4±5.4%. Interestingly, in
another 18 out of the 40 pallidal neurons, ZD7288 increased the firing rate by 137.1±27.6%. Similar bi-directional modulation
on the firing rate was observed by a higher concentration of ZD7288 (0.5 mM) as well as another HCN channel blocker,
CsCl. Furthermore, activation of HCN channels by 8-Br-cAMP increased the firing rate by 63.0±9.3% in 15 out of the 25
pallidal neurons and decreased the firing rateby 46.9±9.4% in another 8 out of the 25 pallidal neurons. Further experiments
revealed that modulation of glutamatergic but not GABAergic transmission may be involved in ZD7288-induced increase in
firing rate. Consistent with electrophysiological results, further studies revealed that modulation of HCN channels also had
bi-directional effects on behavior. Taken together, the present studies suggest that HCN channels may modulate the activity of
pallidal neurons by different pathways in vivo.

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