Rebound excitation triggered by synaptic inhibition in cerebellar nuclear neurons is suppressed by selective T-type calcium channel block

• Following hyperpolarizing inputs, many neurons respond with an increase in firing rate, a phenomenon known as rebound excitation. Rebound excitation has been proposed as a mechanism to encode and process inhibitory signals and transfer them to target structures. Activation of low-voltage-activated T-type calcium channels and the ensuing low-threshold calcium spikes is one of the mechanisms proposed to support rebound excitation. However, there is still not enough evidence that the hyperpolarization provided by inhibitory inputs, particularly those dependent on chloride ions, is adequate to deinactivate a sufficient number of T-type calcium channels to drive rebound excitation on return to baseline. Here, this issue was investigated in the deep cerebellar nuclear neurons (DCNs), which receive the output of the cerebellar cortex conveyed exclusively by the inhibitory Purkinje cells and are also known to display rebound excitation. Using cerebellar slices and whole cell recordings of large DCNs, we show that a novel piperidine-based compound that selectively antagonizes T-type calcium channel activity, 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydropyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide (TTA-P2), suppressed rebound excitation elicited by current injection as well as by synaptic inhibition, whereas other electrophysiological properties of large DCNs were unaltered. Furthermore, TTA-P2 suppressed transient high-frequency rebounds found in DCNs with low-threshold spikes as well as the slow rebounds present in DCNs without low-threshold spikes. These findings demonstrate that chloride-dependent synaptic inhibition effectively triggers T-type calcium channel-mediated rebounds and that the latter channels may support slow rebound excitation in neurons without low-threshold spikes.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Cav3.* channels

cerebellum

chloride inhibition

GABA

postinhibitory rebound

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