Neuroscience
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Alterations in the brain that contribute to the development of epilepsy, also called epileptogenesis, are not well understood, which makes it difficult to develop strategies for preventing epilepsy. Here we have studied the role of the CRE binding transcription factors, cyclic-AMP responsive element modulator (CREM) and inducible cyclic-AMP early repressor (ICER), in the development of epilepsy following pilocarpine induced status epilepticus (SE) in mice. ⋯ Following SE, the CREM/ICER null mice develop a more severe epileptic phenotype experiencing approximately threefold more frequent spontaneous seizures. Together these data suggest that the increase in ICER mRNA following SE may have a role in suppressing the severity of epilepsy.
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The amygdala modulates memory consolidation with the storage of emotionally relevant information and plays a critical role in fear and anxiety. We examined changes in neuronal morphology and neurotransmitter content in the amygdala of rats exposed to a single prolonged stress (SPS) as a putative animal model for human post-traumatic stress disorder (PTSD). Rats were perfused 7 days after SPS, and intracellular injections of Lucifer Yellow were administered to neurons of the basolateral (BLA) and central amygdala (CeA) to analyze morphological changes at the cellular level. ⋯ Double immunostaining by fluorescence and electron microscopy revealed that NPY immunoreactive terminals were closely associated with calcium/calmodulin II-dependent protein kinase (CaMKII: a marker for pyramidal neurons)-positive neurons in the BLA, which were immunopositive to glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). SPS had no significant effect on the expression of CaMKII and MR/GR expression in the BLA. Based on these findings, we suggest that changes in the morphology of pyramidal neurons in the BLA by SPS could be mediated through the enhancement of NPY functions, and this structural plasticity in the amygdala provides a cellular and molecular basis to understand for affective disorders.
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Human studies have shown that a reduction of 5-HT transporter (SERT) increases the vulnerability for anxiety and depression. Moreover, women are more vulnerable to develop depression and anxiety disorders than men. For that reason we hypothesized that homozygous 5-HT transporter knockout rat (SERT(-/-)) models, especially female, are valuable and reliable animal models for humans with an increased vulnerability for anxiety- and depression-related disorders. ⋯ These findings demonstrate that SERT(-/-) rats show anxiety and depression-related behavior, independent of sex. Genetic inactivation of the SERT has apparently such a great impact on behavior, that hardly any differences are found between male and female rats. This knockout rat model may provide a valuable model to study anxiety- and depression-related disorders in male and female rats.
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3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) stimulates the transporter-mediated release of monoamines, including 5-HT. High-dose exposure to MDMA causes persistent 5-HT deficits (e.g. depletion of brain 5-HT) in animals, yet the functional and clinical relevance of such deficits are poorly defined. Here we examine functional consequences of MDMA-induced 5-HT depletions in rats. ⋯ MDMA. As tolerance developed only in rats exposed to high-dose binges, hyperthermia and 5-HT depletion are implicated in this phenomenon. Our results suggest that MDMA tolerance in humans may reflect 5-HT deficits which could contribute to further dose escalation.
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Finely myelinated (type Adelta) and unmyelinated (type C) fibers are the major afferent inputs to spinothalamic tract neurons mediating sensory and reflex responses to noxious and thermal stimuli. These two fiber types differ in their sensory and biophysical properties, raising questions about the interaction of their supraspinal responses. Therefore, we investigated the interaction of cortical responses to stimuli that preferentially excite these fibers in human subjects using evoked potential recordings in a paired conditioning stimulation (CS) and test stimulation (TS) paradigm. ⋯ Furthermore, intra-segmental interaction was differentially effective for Adelta conditioning (peak amplitude, P<0.008; analysis of variance). Our experiments provide the first neurophysiological evidence for a somatotopically distributed, mutually suppressive interaction between cortical responses to preferentially activated Adelta and C afferents in humans. This suppressive interaction of cortical responses suggests contrasting and possibly mutually exclusive sensorimotor functions mediated through the Adelta and C fiber afferent channels.