The Low-Threshold Calcium Channel Cav3.2 Mediates Burst Firing of Mature Dentate Granule Cells

Duménieu, Maël; Senkov, Oleg; Mironov, Andrey; Bourinet, Emmanuel; Kreutz, Michael R.; Dityatev, Alexander; Heisenberg, Martin; Bikbaev, Arthur; Lopez‐Rojas, Jeffrey

doi:10.1093/cercor/bhy084

Cited by 27 publications

(32 citation statements)

References 73 publications

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“…The main electrophysiological difference observed between DLPFC and PPC L3PNs was a higher proportion of bursting L3PNs in DLPFC. Burst firing depends on voltage-gated Ca 2ϩ channels (Williams and Stuart, 1999;Clarkson et al, 2017;Dumenieu et al, 2018) of the T-type Ca V 3 family (Nanou and Catterall, 2018). Therefore, our finding that expression of the Ca V 3 alpha 1G subunit gene CACNA1G was enriched in DLPFC L3PN samples is consistent with the larger proportion of B-L3PNs in DLPFC.…”

Section: Gene Expression Profiles Of L3pns In Dlpfc and Ppcsupporting

confidence: 75%

“…Interestingly, among genes identified as differentially expressed in our microarray analysis is CACNA1G (1.9-fold higher in DLPFC L3PNs). CACNA1G encodes a subunit of the T-type voltage-gated calcium channel fam-ily Ca V 3, involved in the generation of AP bursts in PNs (Williams and Stuart, 1999;Clarkson et al, 2017;Dumenieu et al, 2018). Consistent with the well-known body of data from rodent cortex showing that burst-firing PNs are widely distributed across cortical regions, CACNA1G is expressed in multiple regions of the monkey neocortex (Bernard et al, 2012).…”

Section: Dlpfc and Ppc L3pns Differ In Gene Expression Profilessupporting

confidence: 52%

“…Bursting depends on the activity of T-type voltage-gated Ca 2ϩ channels that show pronounced inactivation at relatively depolarized steady-state membrane potentials (Williams and Stuart, 1999;Clarkson et al, 2017;Dumenieu et al, 2018). Hence, a more depolarized resting membrane potential could inactivate the T-type channels mediating burst firing.…”

Section: Dlpfc L3pns Display Greater Electrophysiological Diversitymentioning

confidence: 99%

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Distinct Properties of Layer 3 Pyramidal Neurons from Prefrontal and Parietal Areas of the Monkey Neocortex

et al. 2019

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In primates, working memory function depends on activity in a distributed network of cortical areas that display different patterns of delay task-related activity. These differences are correlated with, and might depend on, distinctive properties of the neurons located in each area. For example, layer 3 pyramidal neurons (L3PNs) differ significantly between primary visual and dorsolateral prefrontal (DLPFC) cortices. However, to what extent L3PNs differ between DLPFC and other association cortical areas is less clear. Hence, we compared the properties of L3PNs in monkey DLPFC versus posterior parietal cortex (PPC), a key node in the cortical working memory network. Using patch-clamp recordings and biocytin cell filling in acute brain slices, we assessed the physiology and morphology of L3PNs from monkey DLPFC and PPC. The L3PN transcriptome was studied using laser microdissection combined with DNA microarray or quantitative PCR. We found that in both DLPFC and PPC, L3PNs were divided into regular spiking (RS-L3PNs) and bursting (B-L3PNs) physiological subtypes. Whereas regional differences in single-cell excitability were modest, B-L3PNs were rare in PPC (RS-L3PN:B-L3PN, 94:6), but were abundant in DLPFC (50:50), showing greater physiological diversity. Moreover, DLPFC L3PNs display larger and more complex basal dendrites with higher dendritic spine density. Additionally, we found differential expression of hundreds of genes, suggesting a transcriptional basis for the differences in L3PN phenotype between DLPFC and PPC. These data show that the previously observed differences between DLPFC and PPC neuron activity during working memory tasks are associated with diversity in the cellular/ molecular properties of L3PNs.

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Section: Gene Expression Profiles Of L3pns In Dlpfc and Ppcsupporting

confidence: 75%

Section: Dlpfc and Ppc L3pns Differ In Gene Expression Profilessupporting

confidence: 52%

Section: Dlpfc L3pns Display Greater Electrophysiological Diversitymentioning

confidence: 99%

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Distinct Properties of Layer 3 Pyramidal Neurons from Prefrontal and Parietal Areas of the Monkey Neocortex

et al. 2019

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“…Emerging evidence, however, suggests that both T‐type and R‐type voltage‐gated calcium channels are expressed in the AIS of several types of neurons where they may increase the probability of single spikes or contribute to burst firing (Bender & Trussell, ; Dumenieu et al . ). Recent studies also showed that axonal ion channels are targets for neuromodulation.…”

Section: Resultsmentioning

confidence: 97%

Dopamine D2 receptors regulate the action potential threshold by modulating T‐type calcium channels in stellate cells of the medial entorhinal cortex

Jin

Chen

Song

et al. 2019

The Journal of Physiology

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Key pointsr Activation of axonal dopamine D2 receptors (D2Rs) increases action potential (AP) threshold, and thus decreases neuronal excitability in layer II stellate cells of medial entorhinal cortex.r Endogenous dopamine release increases the AP threshold of stellate cells by activating D2Rs. r Activation of D2Rs shifts the activation curve of T-type Ca 2+ channels in a positive direction in a protein kinase A-dependent manner.r Immunofluorescence staining reveals the presence of T-type Ca 2+ channels and D2Rs in the axon initial segments (AISs).r This research makes the pioneering discovery of D2R-induced AP threshold plasticity in AISs of stellate cells. The findings are likely to have significant implications for understanding the cellular processes by which dopamine influences neuronal intrinsic excitability.Abstract Stellate cells in the medial entorhinal cortex (MEC) are considered to constitute the largest population of grid cells, which provide spatial representation to support animal estimation of location. Although dopaminergic fibres from the ventral tegmental area and substantia nigra pars compacta innervate the majority of the cortex, including the MEC, little is known about how dopamine modulates the function of MEC stellate cells. Because dopamine D2 receptors (D2Rs) are involved in spatial cognition and MEC contains high levels of D2Rs, we investigated how D2R activation modulates the neuronal intrinsic excitability of stellate cells. Electrophysiological Xueqin Jin received her bachelor's degree in Pharmaceutical Science in 2014 from Jilin University. Currently, she is a PhD student in the School of Pharmaceutical Sciences at Peking University under the supervision of Prof. Zhuo Huang. She is now focusing on how neurotransmitters modulate neuronal functional plasticity in spatial cognition and working memory.3364 X. Jin and others J Physiol 597.13recordings, optogenetics and molecular biology experiments were performed to investigate the mechanism in mice. Activation of axonal D2Rs, not dendritic or somatic D2Rs, elevated the action potential (AP) threshold and decreased the intrinsic excitability of stellate cells, which was caused by shifting rightward the activation properties of T-type Ca 2+ channels in a D2R-protein kinase A-dependent manner without affecting their steady-state inactivation curve. In support, immunofluorescence assays revealed colocalization of D2Rs and Ca v 3.2 calcium channels within the axon initial segment. These findings are likely to have significant implications for understanding the cellular processes by which dopamine influences neuronal excitability and they may also be applicable to other hippocampal and cortical regions as dopaminergic fibres innervate wide brain regions. Taken together, these findings provide a novel cellular mechanism by which D2Rs modulate AP threshold of stellate cells through T-type Ca 2+ channels in MEC, indicating that D2Rs of MEC play a vital role in modulating the information processing of stellate cells.

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“…Doublet spiking is followed by an AHP which silences electrical activity in motoneurons, and this might facilitate force generation 70 . In mature granule neurons of the dentate gyrus, Cav3.2 supports action potential pairing within tenth of ms, while T-type channel antagonists or Cav3.2 genetic ablation lengthen this interval to no more than 75 ms 71 . In the cerebellum, long term depression at the parallel fiber – Purkinje neuron excitatory synapse is better induced by a fast pairing of parallel fiber stimulation (interval 60 ms) 72 .…”

Section: Discussionmentioning

confidence: 99%

Cav3.2 T-type calcium channels shape electrical firing in mouse Lamina II neurons

Candelas

Reynders

Arango-Lievano

et al. 2019

Sci Rep

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The T-type calcium channel, Cav3.2, is necessary for acute pain perception, as well as mechanical and cold allodynia in mice. Being found throughout sensory pathways, from excitatory primary afferent neurons up to pain matrix structures, it is a promising target for analgesics. In our study, Cav3.2 was detected in ~60% of the lamina II (LII) neurons of the spinal cord, a site for integration of sensory processing. It was co-expressed with Tlx3 and Pax2, markers of excitatory and inhibitory interneurons, as well as nNOS, calretinin, calbindin, PKCγ and not parvalbumin. Non-selective T-type channel blockers slowed the inhibitory but not the excitatory transmission in LII neurons. Furthermore, T-type channel blockers modified the intrinsic properties of LII neurons, abolishing low-threshold activated currents, rebound depolarizations, and blunting excitability. The recording of Cav3.2-positive LII neurons, after intraspinal injection of AAV-DJ-Cav3.2-mcherry, showed that their intrinsic properties resembled those of the global population. However, Cav3.2 ablation in the dorsal horn of Cav3.2 GFP-Flox KI mice after intraspinal injection of AAV-DJ-Cav3.2-Cre-IRES-mcherry, had drastic effects. Indeed, it (1) blunted the likelihood of transient firing patterns; (2) blunted the likelihood and the amplitude of rebound depolarizations, (3) eliminated action potential pairing, and (4) remodeled the kinetics of the action potentials. In contrast, the properties of Cav3.2-positive neurons were only marginally modified in Cav3.1 knockout mice. Overall, in addition to their previously established roles in the superficial spinal cord and in primary afferent neurons, Cav3.2 channel appear to be necessary for specific, significant and multiple controls of LII neuron excitability.

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The Low-Threshold Calcium Channel Cav3.2 Mediates Burst Firing of Mature Dentate Granule Cells

Cited by 27 publications

References 73 publications

Distinct Properties of Layer 3 Pyramidal Neurons from Prefrontal and Parietal Areas of the Monkey Neocortex

Distinct Properties of Layer 3 Pyramidal Neurons from Prefrontal and Parietal Areas of the Monkey Neocortex

Dopamine D2 receptors regulate the action potential threshold by modulating T‐type calcium channels in stellate cells of the medial entorhinal cortex

Cav3.2 T-type calcium channels shape electrical firing in mouse Lamina II neurons

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