Neuroscience
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The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) modulate anxiety and social behaviors. It remains to be elucidated, however, whether direct projections from the BLA to the mPFC play a functional role in these behaviors. ⋯ Furthermore, activation of the BLA-mPFC pathway reduced social interaction in the resident-intruder test, whereas inhibition facilitated social interaction. These results establish a causal relationship between activity in the BLA-mPFC pathway and the bidirectional modulation of anxiety-related and social behaviors.
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The rodent anterior cingulate cortex (ACC) is critical for visceral pain and pain-related aversive response in chronic visceral hypersensitive (VH) state. Long-term potentiation (LTP), induced by theta burst stimulation (TBS) in the medial thalamus (MT)-ACC pathway, is blocked in VH rats. However, the neuronal intrinsic firing characteristics and the MT-ACC connectivity have not been investigated in visceral pain. ⋯ Neural spike activity in the ACC becomes synchronized with ongoing theta oscillations of LFP. Furthermore, cross correlation analysis showed augmented synchronization of thalamo-ACC theta band LFPs, which was consistent with an increase of neuronal communication between the two regions. In conclusion, these results reveal theta oscillations and theta-frequency phase-locking as prominent features of neural activity in the ACC and a candidate neural mechanism underlying acute visceral pain.
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While amyloid beta (Aβ) plays a central role in the development of Alzheimer's disease (AD), recent evidence suggests the involvement of arginine metabolism in AD pathogenesis. Earlier research has shown that a single intracerebroventricular (i.c.v.) infusion of pre-aggregated Aβ25-35 (the neurotoxic domain of the full-length Aβ) altered arginine metabolism in the rat hippocampus (particularly the CA2/3 and dentate gyrus (DG) sub-regions) and prefrontal cortex (PFC) at the time point of 8 days post-infusion. The present study measured the levels of L-arginine and its nine downstream metabolites (L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine, glutamate, GABA and glutamine) in the hippocampus and PFC at the time points of 42 and 97 days following a single bilateral i.c.v. infusion of Aβ25-35 (30 nmol/rat) or Aβ35-25 (reverse peptide; 30 nmol/rat). ⋯ At the 97-day time point, however, there were decreased L-ornithine, GABA and putrescine levels, but increased glutamate/GABA ratio, in the PFC and increased spermine levels in the DG sub-region. Cluster analyses showed that L-arginine and its three main metabolites L-citrulline, L-ornithine and agmatine formed distinct groups, which changed as a function of Aβ25-35 at the 42-day and 97-day time points, particularly in the CA2/3 and PFC regions respectively. This study, for the first time, demonstrates that a single i.c.v. infusion of pre-aggregated Aβ25-35 leads to prolonged alterations in arginine metabolism in a region-specific and time-dependent manner, which further supports the involvement of arginine metabolism in AD pathogenesis.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder for which there is currently no effective treatment. Studies indicate that enhancing autophagy in mouse models of neurodegenerative disease can ameliorate the behavioral symptoms and pathological damage associated with the accumulation of pathological mutant proteins such as mutant superoxide dismutase (SOD1). This study investigated the effects of trehalose treatment on both early and end-stage disease in a transgenic mouse model of ALS via short-term (30 days after administration) and long-term (from 60 days after administration to death) trehalose treatment experiments. ⋯ Furthermore, trehalose treatment significantly postponed disease onset, lengthened the time it took to reach a neurological score of 2 and preserved motor function; however, trehalose became less effective at delaying further disease progression as the disease progressed beyond a neurological score of 2 and it failed to extend the survival of SOD1-G93A transgenic mice. Additionally, independent of autophagy, trehalose consistently inhibited microgliosis and astrogliosis throughout the entire duration of the study. In conclusion, trehalose may be a useful add-on therapy in conjunction with other ALS treatment options to alleviate symptoms in early-stage ALS.
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Anatomical studies have demonstrated that hypocretinergic and GABAergic neurons innervate cells in the nucleus pontis oralis (NPO), a nucleus responsible for the generation of active (rapid eye movement (REM)) sleep (AS) and wakefulness (W). Behavioral and electrophysiological studies have shown that hypocretinergic and GABAergic processes in the NPO are involved in the generation of AS as well as W. An increase in hypocretin in the NPO is associated with both AS and W, whereas GABA levels in the NPO are elevated during W. ⋯ In addition, hypocretin-1 also blocked GABAergic inhibition of EPSPs evoked by stimulation of the laterodorsal tegmental nucleus. These data indicate that hypocretin and GABA function within the context of a neuronal gate that controls the activity of AS-on neurons. Therefore, we suggest that the occurrence of either AS or W depends upon interactions between hypocretinergic and GABAergic processes as well as inputs from other sites that project to AS-on neurons in the NPO.