Neuroscience
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The plasticity of nervous systems allows animals to quickly adapt to a changing environment. In particular, seasonal plasticity of brain structure and behavior is often critical to survival or mating in seasonal climates. Songbirds provide striking examples of seasonal changes in neural circuits and vocal behavior and have emerged as a leading model for adult brain plasticity. ⋯ On the contrary, lesions did not affect singing behavior during the breeding season. Our results therefore indicate that the BG-forebrain pathway introduces acoustic and syntactic variability in song when canaries resume singing in early fall. We propose that BG-forebrain circuits actively participate in seasonal plasticity by injecting variability in behavior during non-breeding season.
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Prolonged low-level noise exposure alters loudness perception in humans, presumably by decreasing the gain of the central auditory system. Here we test the central gain hypothesis by measuring the acute and chronic physiologic changes at the level of the cochlea and inferior colliculus (IC) after a 75-dB SPL, 10-20-kHz noise exposure for 5weeks. The compound action potential (CAP) and summating potential (SP) were used to assess the functional status of the cochlea and 16 channel electrodes were used to measure the local field potentials (LFP) and multi-unit spike discharge rates (SDR) from the IC immediately after and one-week post-exposure. ⋯ Surprisingly, one-week post-exposure supra-threshold responses from the cochlea had not only recovered, but were significantly larger than normal, and thresholds were significantly better than controls. Moreover, sound-evoked hyperactivity in the IC was sustained within the noise exposure frequency band but suppressed at higher frequencies. When response amplitudes representing the neural output of the cochlea and IC activity at one-week post exposure were compared with control animal responses, a central attenuation phenomenon becomes evident, which may play a key role in understanding why low-level noise can sometimes ameliorate tinnitus and hyperacusis percepts.
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Diffuse traumatic brain injury (TBI) initiates secondary pathology, including inflammation and reduced myelination. Considering these injury-related pathologies, the many states of activated microglia as demonstrated by differing morphologies would form, migrate, and function in and through fields of growth-inhibitory myelin byproduct, specifically Nogo. Here we evaluate the relationship between inflammation and reduced myelin antigenicity in the wake of diffuse TBI and present the hypothesis that the Nogo-66 receptor antagonist peptide NEP(1-40) would reverse the injury-induced shift in distribution of microglia morphologies by limiting myelin-based inhibition. ⋯ By 7d post-injury, no differences in the distributions of microglia were noted between vehicle and NEP(1-40). This study begins to link secondary pathologies of white matter damage and inflammation after diffuse TBI. In the injured brain, secondary pathologies co-occur and likely interact, with consequences for neuronal circuit disruption leading to neurological symptoms.
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DiGeorge/22q11.2 Deletion Syndrome (22q11DS) is a common genetic microdeletion syndrome that underlies several neurodevelopmental disorders including autism, attention deficit/hyperactivity disorder, and schizophrenia. In addition to cognitive impairments, those with 22q11DS have disrupted feeding and swallowing from birth onward. This perinatal dysphagia significantly compromises nutritional status, impairs appropriate weight gain, and can lead to life threatening aspiration-based infections. ⋯ Hypoglossal motor neurons from LgDel mouse pups have action potentials with afterhyperpolarizations, mediated by a large conductance charybdotoxin-sensitive Ca-activated K current, that are significantly shorter in duration and greater in magnitude than those in wild-type pups. In addition, the amplitude, but not frequency, of glutamatergic excitatory glutamatergic postsynaptic currents (EPSCs) is diminished, and GABAergic, but not glycinergic, neurotransmission to hypoglossal motor neurons was reduced in LgDel animals. These observations provide a foundation for understanding the neurological changes in hypoglossal motor neuron function and their contribution to swallowing abnormalities that occur in DiGeorge/22q11.2 Deletion Syndrome.
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The role of Celsr3 in the development of central somatosensory projections from dorsal root ganglia.
Dorsal root ganglion (DRG) neurons receive peripheral somatosensory information and send orderly projections to second-order relay nuclei in the spinal cord and in the brainstem. Atypical cadherin Celsr3 is known to play a critical role in wiring of several central and peripheral axons. Although Celsr3 mRNA is heavily expressed in DRG neurons, its role in the development of somatosensory projections remains unexplored. ⋯ Furthermore, more Pavalbumin-positive fibers invaded the gray matter and made more contacts with spinal motor neurons in mutant than in control samples. Behavioral analysis showed that mutant animals were less sensitive to pain and more sensitive to mechanical stimulation than controls. In conclusion, Celsr3 is dispensable for the patterning of central DRG projections, but it regulates for the fine mapping of sensory fibers in the gray matter, which is important for somatosensory processing.