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H‐current blocker (ZD 7288) reduces firing patterns on putative dopaminergic neurons of the Ventral Tegmental Area

The hyperpolarization‐activated cation current (H‐current) is a major determinant of neuronal intrinsic excitability in various cells including dopaminergic neurons of the Ventral Tegmental Area (VTA DA). In contrast to other cellular conductances, the H‐current activates through hyperpolarizing voltage steps to potentials negative to −55mV and depolarizes the membrane potential. We explored through in vivo anesthetized single unit extracellular electrophysiology the contribution of the H‐current on VTA DA neurons spontaneous firing patterns in naïve rats. A key feature of evaluating spontaneous excitability is the detection of bursting activity. Bursting is defined as trains of two or more spikes occurring within a short interval and followed by a prolonged period of inactivity (Grace et al., 1984). It has been well documented that burst formation increases the reliability of information transfer. Additionally, bursts and spikes can develop a parallel code, in which they can promote various stimulus features in the same spike train. To elucidate the contribution of H‐current on VTA DA neurons spontaneous firing patterns we perfused H‐current blocker (ZD 7288) through a double barrel pipette and evaluated its effect. H‐current blockade significantly reduced firing rate, bursting frequency and percent of spikes in burst in VTA DA neurons. Neuroadaptations in this network are hypothesized to trigger various neurobiological diseases including drug addiction. Reduction of spontaneous firing patterns through H‐current blockade could serve as a possible modulator of conditions related to VTA DA hyperexcitability.