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

Abstract

Albéri L, Lintas A, Kretz R, Schwaller B, Villa AE. The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons. J Neurophysiol 109: 2827-2841, 2013. First published March 13, 2013 doi:10.1152/jn.00375.2012.-The reticular thalamic nucleus (RTN) of the mouse is characterized by an overwhelming majority of GABAergic neurons receiving afferences from both the thalamus and the cerebral cortex and sending projections mainly on thalamocortical neurons. The RTN neurons express high levels of the "slow Ca buffer" parvalbumin (PV) and are characterized by low-threshold Ca 2ϩ currents, I T . We performed extracellular recordings in ketamine/ xylazine anesthetized mice in the rostromedial portion of the RTN. In the RTN of wild-type and PV knockout (PVKO) mice we distinguished four types of neurons characterized on the basis of their firing pattern: irregular firing (type I), medium bursting (type II), long bursting (type III), and tonically firing (type IV). Compared with wild-type mice, we observed in the PVKOs the medium bursting (type II) more frequently than the long bursting type and longer interspike intervals within the burst without affecting the number of spikes. This suggests that PV may affect the firing properties of RTN neurons via a mechanism associated with the kinetics of burst discharges. Ca v 3.2 channels, which mediate the I T currents, were more localized to the somatic plasma membrane of RTN neurons in PVKO mice, whereas Ca v 3.3 expression was similar in both genotypes. The immunoelectron microscopy analysis showed that Ca v 3.2 channels were localized at active axosomatic synapses, thus suggesting that the differential localization of Ca v 3.2 in the PVKOs may affect bursting dynamics. Cross-correlation analysis of simultaneously recorded neurons from the same electrode tip showed that about one-third of the cell pairs tended to fire synchronously in both genotypes, independent of PV expression. In summary, PV deficiency does not affect the functional connectivity between RTN neurons but affects the distribution of Ca v 3.2 channels and the dynamics of burst discharges of RTN cells, which in turn regulate the activity in the thalamocortical circuit.

Mice lacking the transcriptional coactivator PGC-1α exhibit alterations in inhibitory synaptic transmission in the motor cortex

“…These changes in PV+ cell firing rate could be caused by changes in metabolic genes regulated by PGC-1α (Finck and Kelly 2006); there is abundant evidence for a high metabolic requirement for cortical PV+ interneurons (reviewed in (Jiang, Cowell et al 2013)). A loss of PV itself could contribute to the decreased firing rate, as loss of the calcium buffer in PV knockout mice has been shown to alter intrinsic excitability of GABAergic neurons in the reticular thalamic nucleus (Alberi, Lintas et al 2013). However it is also possible that other factors contribute to this reduction.…”

The effect of parvalbumin deficiency on the acoustic startle response and prepulse inhibition in mice

“…Previous animal studies have shown that for PPI of ASR, several pathways are implicated including direct glutamatergic projections from the cochlear nuclei, inhibitory cholinergic projections from the pedunculopontine tegmental nucleus and indirect inputs from the superior and inferior colliculi [15]. Electrophysiological recordings of cortical, hippocampal and cerebellar neuronal activity in PV−/− mice in vitro showed that the absence of PV in a subpopulation of GABA-ergic interneurons resulted in modification of the dynamics of inhibitory control (for reviews, see [22]), enhancement of the severity of pharmacologically-induced seizures [25], alterations of Purkinje cell-firing [26], and modulation of the firing properties of the reticular thalamic nucleus bursting neurons [1]. Fast-spiking PV-positive inhibitory cells, which represent the largest inhibitory subpopulation in the auditory cortex of the cat, are involved in the sharpening of frequency and intensity tuning and the shaping of spectral modulation preferences [27,31].…”

Discharge properties of neurons recorded in the parvalbumin-positive (PV1) nucleus of the rat lateral hypothalamus

“…Parvalbumin is a Ca 2+ buffer protein characterized by a slow-onset Ca 2+ binding that generally does not affect the initial amplitude of Ca 2+ transients, but then accelerates the early phase of the intracellular Ca 2+ concentration, thus affecting short-term plasticity and controlling the intracellular Ca 2+ available to SK channels [30]. Loss of PV leads to enhanced susceptibility to epileptic seizure [12] and modifications of the firing patterns at the thalamocortical level [13,15]. The question is raised whether firing patterns other than the regular firing correspond to distinct cell populations, maybe lying in the border of the nucleus, or whether they are generated by cells that are in a different functional state.…”

“…However, it is worth reporting that lesions of PAG affect states of consciousness [36] and that PAG receives afferences from the prefrontal cortex [37] and projects to intralaminar and midline thalamic nuclei [38]. Moreover, PV is highly expressed in the thalamic reticular nucleus [13] which plays a key role in 'gating' consciousness [39]. These observations taken together with the present findings may suggest that the activity of PV1-nucleus regulates psychomotor functions in the framework of an extended reticular thalamic activating system.…”

“…It is interesting to notice that elsewhere in the brain PV-stained neurons correspond to GABAergic cells [3] mediating an inhibitory effect through GABA(A) receptors, thus exerting a regulatory function, either via a direct inhibition or an indirect disinhibition [10]. Hence, GABAergic neurons and PV are generally associated and their role in controlling synaptic plasticity, modulating the firing pattern, and the spiketiming-dependent plasticity has been clearly established [11][12][13][14][15]. The fact that the PV1-nucleus is likely to be composed by glutamatergic cells expressing PV and that its main target is a well delimited column of cells on the edge of the ipsilateral PAG raises the question whether its function is to integrate, relay and transmit an information or rather to regulate the activity of the target cells.…”