Involvement of the Cav3.2 T-Type Calcium Channel in Thalamic Neuron Discharge Patterns

Abstract

BackgroundMice that have defects in their low-threshold T-type calcium channel (T-channel) genes show altered pain behaviors. The changes in the ratio of nociceptive neurons and the burst firing property of reticular thalamic (RT) and ventroposterior (VP) neurons in Cav3.2 knockout (KO) mice were studied to test the involvement of thalamic T-channel and burst firing activity in pain function.ResultsUnder pentobarbital or urethane anesthesia, the patterns of tonic and burst firings were recorded in functionally characterized RT and VPL neurons of Cav3.2 KO mice. Many RT neurons were nociceptive (64% under pentobarbital anesthesia and 50% under urethane anesthesia). Compared to their wild-type (WT) controls, fewer nociceptive RT neurons were found in Cav3.2 KO mice. Both nociceptive and tactile RT neurons showed fewer bursts in Cav3.2 KO mice. Within a burst, RT neurons of Cav3.2 KO mice had a lower spike frequency and less-prominent accelerando-decelerando change. In contrast, VP neurons of Cav3.2 KO mice showed a higher ratio of bursts and a higher discharge rate within a burst than those of the WT control. In addition, the long-lasting tonic firing episodes in RT neurons of the Cav3.2 KO had less stereotypic regularity than their counterparts in WT mice.ConclusionsRT might be important in nociception of the mouse. In addition, we showed an important role of Cav3.2 subtype of T-channel in RT burst firing pattern. The decreased occurrence and slowing of the bursts in RT neurons might cause the increased VP bursts. These changes would be factors contributing to alternation of pain behavior in the Cav3.2 KO mice.

The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons

“…This observation could be explained by the use of the anesthetic drug ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist (Gunduz-Bruce 2009) that is likely to affect the specific NMDA currents in PV-positive interneurons (Korotkova et al 2010). In contrast to the previous study of in vivo recording in the RTN by Liao et al (2011) we observed lower firing rates (on average, 3.7 vs. 8.6 spikes/ s). In addition to the differences in the anesthetic procedures mentioned above, our studies differed in the type of electrodes that were used, in the sorting procedure of the waveforms of the electrophysiological signals, and in the sample size (n ϭ 93 in this study vs. n ϭ 17).…”

“…This might be caused either by the absence of PV or by the homeostatic compensation mechanisms underlying the altered cellular distribution of Ca v 3.2. Interestingly, the firing phenotype of PVKO RTN neurons showed large similarities to the one seen in Ca v 3.2 KO neurons (Liao et al 2011): the burst duration was increased, caused by a larger interval between spikes, without affecting the spike number within a burst. Ablation of the Ca v 3.2 channel, a LVA channel type characterized by fast activation and inactivation kinetics (Kozlov et al 1999), provokes I T to be mediated by the "slower" variant, Ca v 3.3, hence leading to the observed phenotype.…”

“…This, in turn, may affect the kinetics of activation of SK channels as well as Ca 2ϩ uptake and extrusion systems. Another possibility is that a putative reduction in dendritic vs. somatic expression of Ca v 3.2 favors the activation of the slower Cav3.3 channels in dendrites leading to a situation resembling the one reported in the Ca v 3.2 KO mice (Liao et al 2011). Altogether in KO mice for the various Ca 2ϩ signaling components, Ca v 3.2, Ca v 3.3, SK2, and PV, the firing properties of those neurons are profoundly affected.…”

“…The present study presents in vivo recordings of RTN neurons in ketamine anesthetized mice, for the first time to our knowledge. The only other study reporting in vivo RTN extracellular single unit recording from mice was performed under pentobarbital and urethane anesthesia (Liao et al 2011). In rats, in vivo recordings of RTN neurons were performed under pentobarbital, urethane, ketamine, or halothane anesthesia aiming primarily to study the comparative response to nociceptive stimuli in RTN and in the ventroposterior lateral nucleus of the thalamus (Yen and Shaw 2003).…”

“…Based on the commonalities of the PVKO and Ca v 3.2 KO phenotype (Liao et al 2011) with respect to RTN bursting firing properties we investigated the possibility that in the absence of PV alteration in Ca v 3.2 and Ca v 3.3 channel distribution and/or expression may occur in RTN neurons. To restrict our analysis to "PV-ir" RTN neurons also in the absence of PV, we took advantage of a transgenic mouse line that expresses EGFP under the control of the PV promoter (gene symbol: Pvalb) (Meyer et al 2002).…”