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Molecular switch from L-type Ca v 1.3 to Ca v 1.2 Ca2+ channel signaling underlies long-term psychostimulant-induced behavioral and molecular plasticity.

ABSTRACT: L-type Ca(2+) channel (LTCC)-activated signaling cascades contribute significantly to psychostimulant-induced locomotor sensitization; however, the precise contribution of the two brain-specific subunits Ca(v)1.2 and Ca(v)1.3 remains mostly unknown. In this study, by using amphetamine and cocaine locomotor sensitization in mutant mice expressing dihydropyridine (DHP)-insensitive Ca(v)1.2 LTCCs (Ca(v)1.2DHP(-/-)), we find that, as opposed to a previously identified role of the Ca(v)1.3 subunit of LTCCs in development of sensitization, the Ca(v)1.2 subunit mediates expression of amphetamine and cocaine sensitization when examined after a 14 d drug-free period. Molecular studies to further elucidate the role of Ca(v)1.2 versus Ca(v)1.3 LTCCs in activating signaling pathways in the nucleus accumbens (NAc) of drug-naive versus drug-preexposed mice examined 14 d later revealed that an acute amphetamine and cocaine challenge in drug-naive mice increases Ser133 cAMP response element-binding protein (CREB) phosphorylation in the NAc via Ca(v)1.3 channels and via a dopamine D(1)-dependent mechanism, independent of the extracellular signal-regulated kinase (ERK) pathway, an important mediator of psychostimulant-induced plasticity. In contrast, in amphetamine- and cocaine-preexposed mice, an amphetamine or cocaine challenge no longer activates CREB unless Ca(v)1.2 LTCCs are blocked. This Ca(v)1.2-dependent blunting of CREB activation that underlies expression of locomotor sensitization occurs only after extended drug-free periods and involves recruitment of D(1) receptors and the ERK pathway. Thus, our results demonstrate that specific LTCC subunits are required for the development (Ca(v)1.3) versus expression (Ca(v)1.2) of psychostimulant sensitization and that subunit-specific signaling pathways recruited by psychostimulants underlies long-term drug-induced behavioral responses.

SUBMITTER: Giordano TP

PROVIDER: S-EPMC3077109 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Molecular switch from L-type Ca v 1.3 to Ca v 1.2 Ca2+ channel signaling underlies long-term psychostimulant-induced behavioral and molecular plasticity.

Giordano Thomas P TP Tropea Thomas F TF Satpute Shirish S SS Sinnegger-Brauns Martina J MJ Striessnig Joerg J Kosofsky Barry E BE Rajadhyaksha Anjali M AM

The Journal of neuroscience : the official journal of the Society for Neuroscience 20101201 50

L-type Ca(2+) channel (LTCC)-activated signaling cascades contribute significantly to psychostimulant-induced locomotor sensitization; however, the precise contribution of the two brain-specific subunits Ca(v)1.2 and Ca(v)1.3 remains mostly unknown. In this study, by using amphetamine and cocaine locomotor sensitization in mutant mice expressing dihydropyridine (DHP)-insensitive Ca(v)1.2 LTCCs (Ca(v)1.2DHP(-/-)), we find that, as opposed to a previously identified role of the Ca(v)1.3 subunit of ...[more]

PMID: 21159975

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Project description:Background The detection of environmental cues and signals via the sensory system directs behavioral choices in diverse organisms. Insect larvae rely on input from the chemosensory system, mainly olfaction, for locating food sources. In several lepidopteran species, foraging behavior and food preferences change across larval instars; however, the molecular mechanisms underlying such behavioral plasticity during larval development are not fully understood. Here, we hypothesize that expression patterns of odorant receptors (ORs) change during development, as a possible mechanism influencing instar-specific olfactory-guided behavior and food preferences. Results We investigated the expression patterns of ORs in larvae of the cotton leafworm Spodoptera littoralis between the first and fourth instar and revealed that some of the ORs show instar-specific expression. We functionally characterized one OR expressed in the first instar, SlitOR40, as responding to the plant volatile, β-caryophyllene and its isomer α-humulene. In agreement with the proposed hypothesis, we showed that first but not fourth instar larvae responded behaviorally to β-caryophyllene and α-humulene. Moreover, knocking out this odorant receptor via CRISPR-Cas9, we confirmed that instar-specific responses towards its cognate ligands rely on the expression of SlitOR40. Conclusion Our results provide evidence that larvae of S. littoralis change their peripheral olfactory system during development. Furthermore, our data demonstrate an unprecedented instar-specific behavioral plasticity mediated by an OR, and knocking out this OR disrupts larval behavioral plasticity. The ecological relevance of such behavioral plasticity for S. littoralis remains to be elucidated, but our results demonstrate an olfactory mechanism underlying this plasticity in foraging behavior during larval development. Supplementary Information The online version contains supplementary material available at 10.1186/s12915-021-01159-1.

Dataset Information

Molecular switch from L-type Ca v 1.3 to Ca v 1.2 Ca2+ channel signaling underlies long-term psychostimulant-induced behavioral and molecular plasticity.

Publications

Molecular switch from L-type Ca v 1.3 to Ca v 1.2 Ca2+ channel signaling underlies long-term psychostimulant-induced behavioral and molecular plasticity.

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