Neuroscience
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The μ-opioid receptor (MOR) and dopamine D1 receptor are co-expressed in the medium spiny neurons of striatal areas and the signaling pathways activated by these two receptors are in functional competition. However, in certain conditions an integrated response mediated by the dopamine D1 receptor transduction system is observed. In mice, morphine administration induces hypermotility and this response has been described in terms of a β-arrestin2-dependent mechanism that favors prevalent dopamine D1 receptor activation. ⋯ We then examined MOR-dopamine D1 receptor interactions after sucrose consumption. Sucrose increased NAcS dopamine D1 receptor signaling in NFD and FD rats, and a reduction in β-arrestin2 expression prevented this effect selectively in FD rats. These results show the β-arrestin2-dependent prevalence of dopamine D1 receptor signaling in response to acute morphine or sucrose consumption elicited by food deprivation in rats.
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The mechanism of action of botulinum neurotoxin type A (BoNT/A) is well characterized, but some published evidence suggests the potential for neuronal retrograde transport and cell-to-cell transfer (transcytosis) under certain experimental conditions. The present study evaluated the potential for these processes using a highly selective antibody for the BoNT/A-cleaved substrate (SNAP25197) combined with 3-dimensional imaging. SNAP25197 was characterized in a rat motor neuron (MN) pathway following toxin intramuscular injections at various doses to determine whether SNAP25197 is confined to MNs or also found in neighboring cells or nerve fibers within spinal cord (SC). ⋯ Therefore, under the present experimental conditions, our results suggest that BoNT/A is confined to MNs and any evidence of distal activity is due to limited systemic spread of the toxin at higher doses and not through transcytosis within SC. Lastly, at higher doses of BoNT/A, SNAP25197 was expressed throughout MNs and colocalized with synaptic markers on the plasma membrane at 6 days post-treatment. These data support previous studies suggesting that SNAP25197 may be incorporated into SNARE-protein complexes within the affected MNs.
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Functions of the hippocampus are segregated along its long axis and emerging evidence shows that the local circuitry is specialized accordingly. Sharp waves (SPWs) and ripples are a basic hippocampal network activity implicated in memory processing. Using recordings from the CA1 field of both dorsal (DH) and ventral (VH) rat hippocampal slices we found that SPWs are larger, shorter and occur much more frequently in the VH than in the DH. ⋯ Isolated unit complex spike bursts display a significantly lower number of spikes and longer inter-spike intervals in the VH than in the DH suggesting that the synaptically driven neuronal excitability is lower in the VH. We propose that to some extent these differences result from the relatively higher network excitability of the VH compared with DH. Furthermore, they might reflect specializations that provide the local circuitries of the DH and VH with the required optimal ability for synaptic plasticity and might also suggest that the VH could be a favored site of SPW-Rs initiation.
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The immune/inflammatory signaling molecule tumor necrosis factor α (TNFα) is an important mediator of both constitutive and plastic signaling in the brain. In particular, TNFα is implicated in physiological processes, including fever, energy balance, and autonomic function, known to involve the hypothalamic paraventricular nucleus (PVN). Many critical actions of TNFα are transduced by the TNFα type 1 receptor (TNFR1), whose activation has been shown to potently modulate classical neural signaling. ⋯ Dendritic profiles expressing TNFR1 were contacted by axon terminals, which formed non-synaptic appositions, as well as excitatory-type and inhibitory-type synaptic specializations. A smaller population of TNFR1-labeled axon terminals making non-synaptic appositions, and to a lesser extent synaptic contacts, with unlabeled dendrites was also identified. These findings indicate that TNFR1 is structurally positioned to modulate postsynaptic signaling in the PVN, suggesting a mechanism whereby TNFR1 activation contributes to cardiovascular and other autonomic functions.
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A number of studies have shown that sensory inputs from the hand can have a profound effect in stabilizing upright posture. This suggests that the central nervous system can extract information about body motion and external forces acting on the body from cutaneous sensory signals. ⋯ In this study we investigate whether this rapid change in activation of lower limb muscles is an invariant response determined by the pattern of somatosensory information arising from sensory receptors in the hand or whether it adapts to changes in postural stability. We manipulated lateral stability of upright stance by changing stance width which had no effect on the activation of upper limb muscles or hand kinematics, but produced profound changes in the activation patterns of lower limb muscles when perturbations were in the medial/lateral direction without affecting the activation patterns of muscles when perturbations were in the anterior/posterior direction.