Publications by authors named "Julie Pepin"

Article Synopsis
  • This study investigates the CACNA1A gene mutations linked to developmental epileptic encephalopathies (DEEs) in children, focusing on their diverse genetic impacts.
  • Four specific de novo mutations were analyzed, revealing two (G230V and I1357S) cause loss-of-function effects, while two others (A713T and V1396M) exert gain-of-function effects on calcium channel activity.
  • The research emphasizes the importance of functional validation of these mutations to understand DEE pathways better and inform potential therapeutic approaches.
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Hippocampal interneurons synchronize the activity of large neuronal ensembles during memory consolidation. Although the latter process is manifested as increases in synaptic efficacy which require new protein synthesis in pyramidal neurons, it is unknown whether such enduring plasticity occurs in interneurons. Here, we uncover a long-term potentiation (LTP) of transmission at individual interneuron excitatory synapses which persists for at least 24 h, after repetitive activation of type-1 metabotropic glutamate receptors [mGluR1-mediated chemical late LTP (cL-LTP(mGluR1))].

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Introduction: Constrictive remodeling of the neointima results in the late lumen loss and restenosis after balloon angioplasty. Intense expression of alpha8beta1 integrin in the contractile state of vascular smooth muscle cells (VSMCs) and in myofibroblasts led us to hypothesize that it might be involved in the process of late constrictive remodeling.

Methods And Results: Balloon injury was used to induce neointima formation in the rat carotid artery.

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The behavioral consequences of uncontrollable stress that are collectively called learned helplessness (LH) are mediated in part by increased levels of serotonin (5-HT) activity in the dorsal raphe nucleus (DRN) and it's projection regions. Recently, corticotropin-releasing hormone (CRH) within the DRN has been implicated in the development of LH because intra-DRN CRH produces LH at very high doses, and because intra-DRN antagonists for the CRH 2 receptor (CRHR2) block LH. Since these behavioral effects are mediated by both 5-HT excitation and CRHR2 activation, we have suggested that CRHR2 mediates excitation of DRN 5-HT neurons.

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Rationale: Exposure to a single session of uncontrollable inescapable shock (IS), but not to identical controllable escapable shock, produces a potentiation of morphine's rewarding properties that is unusual in that the stressor can be given a number of days before the drug administration in an environment quite different from the drug context. Many other behavioral outcomes of stressors that depend on the uncontrollability of the stressor are mediated by alterations in serotonergic (5-HT) neurons within the dorsal raphe nucleus (DRN).

Objectives: The present experiments examined the role of the DRN and 5-HT in mediating the effect of IS on the rewarding properties of morphine as assessed by conditioned place preference (CPP).

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It has previously been shown that inescapable (IS) but not escapable (ES) stress potentiates the rewarding properties of morphine as measured by conditioned place preference and psychomotor activation, and that this potentiation may be mediated by dorsal raphe nucleus (DRN) serotonin (5-HT) neurons. The medial prefrontal cortex (mPFC) has been implicated in both reward and stress, and is a projection region of the DRN. The mPFC also contains dopaminergic afferents from the ventral tegmental area, which has been the focus of many studies exploring both the rewarding properties of drugs and the aversive properties of stress.

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We have recently demonstrated that exposure to a single session of inescapable shock (IS), but not to identical amounts and distributions of escapable shock (ES), increases the rewarding properties of morphine, as measured by conditioned place preference (CPP). Interestingly, we also found that exposure to IS has no effect, or even interferes with amphetamine CPP. The present study explored whether the potentiating effect of IS on morphine reward, but not amphetamine reward, would generalize to the locomotor properties of these drugs.

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