Neuroscience
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Anhedonia is a core symptom of clinical depression. Two brain neuropeptides that have been implicated in anhedonia symptomology in preclinical depression models are dynorphin and orexin; which are concentrated along lateral hypothalamic dopamine reward pathways. These affect regulating neuropeptides modulate each other's function, implicating an interactive dysfunction between them in anhedonia symptomology. ⋯ But orexin was reduced in the VTA and mPFC. Also, dynorphin and orexin were both diminished in the hypothalamus which is noteworthy since nearly all hypothalamic orexin cells co-express dynorphin. These findings suggest that orexin and dynorphin function may be imbalanced between the hypothalamus and mesocortical dopaminergic brain regions in depression.
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L-arginine, a semi-essential amino acid, can be metabolized to form a number of bioactive molecules. Nitric oxide (NO), generated by NO synthase (NOS) from L-arginine, has been strongly implicated in the aging process. Agmatine, decarboxylated arginine, regulates the production of NO and other metabolites of L-arginine, modulates behavioural function, and has anti-inflammatory and neuroprotective effects. ⋯ Agmatine (40 mg/kg) administered intraperitoneally significantly improved spatial working memory and object recognition memory in aged rats, suppressed age-related elevation in total NOS activity, and restored endothelial NOS protein to the normal level. However, agmatine supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings suggest that exogenous agmatine selectively improves behavioural function in aged rats under the present experimental condition, and merit future investigation of its therapeutic potential in cognitive decline during aging.
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The parabrachial nucleus (PB) is a brainstem cell group that receives a strong input from the nucleus tractus solitarius regarding the physiological status of the internal organs and sends efferent projections throughout the forebrain. Since the neuroanatomical organization of the PB remains unclear, our first step was to use specific antibodies against two neural lineage transcription factors: Forkhead box protein2 (FoxP2) and LIM homeodomain transcription factor 1 beta (Lmx1b) to define the PB in adult rats. This allowed us to construct a cytoarchitectonic PB map based on the distribution of neurons that constitutively express these two transcription factors. ⋯ The Kölliker-Fuse nucleus as well as the lateral crescent PB and rostral-most part of the PBcl contain neurons that co-express FoxP2+ and Lmx1b+, but none of these were activated after blood pressure changes. Salt-sensitive FoxP2 neurons in the pre-locus coeruleus and PBel-inner were not c-Fos activated following blood pressure changes. In summary, the present study shows that the PBel-outer and PBcl subnuclei originate from two different neural progenitors, contain glutamatergic neurons, and are affected by blood pressure changes, with the PBel-outer reacting to both hypo- and hypertension, and the PBcl signaling only hypotensive changes.
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For midbrain dopamine (DA) neurons to respond to sensory events, the presence of a stimulus must first be detected. Where is the signal that activates DA neurons coming from? Here we show that DA responses to a vibrotactile stimulus lag significantly behind those of the primary somatosensory cortex, but they arise with a latency that closely matches the onset of premotor neurons known to encode perceptual decisions. In agreement with previous findings, these data suggest that sensory evoked DA activity does not signal a stimulus physical presence but arises from the output of a perceptual decision.
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Perineuronal nets (PNNs) are lattice-like substructures of the neural extracellular matrix that enwrap particular populations of neurons throughout the central nervous system. Previous work suggests that this structure plays a major role in modulating developmental neural plasticity and brain maturation. Understanding the precise role of these structures has been hampered by incomplete comprehension of their molecular composition and cellular contributions to their formation, which is studied herein using primary cortical cell cultures. ⋯ Interestingly, in the absence of these glial-derived components, an aggrecan- and hyaluronan-reactive PNN developed, demonstrating that these two components are sufficient for base PNN assembly. Other components were expressed in a glial-dependent manner. Overall, this work provides deeper insight into the complex interplay between neurons and glia in the formation of the PNN and improves our understanding of the molecular composition of these structures.