Neuroscience
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Step initiation is associated with anticipatory postural adjustments (APAs) that vary according to the speed of the first step. When step initiation is elicited by a "go" signal (i.e. in a reaction time task), the presentation of an unpredictable, intense, acoustic startling stimulus (engaging a subcortical mechanism) simultaneously with or just before the imperative "go" signal is able to trigger early-phase APAs. The aim of the present study was to better understand the mechanisms underlying APAs during step initiation. ⋯ Depending on the intensity of the stimulus, APAs prior to step initiation can be triggered without the evocation of a startle response or an acoustic blink. Greater reaction times for these APAs were observed for non-startling stimuli. This observation suggested the involvement of pathways that did not involve the brainstem as a "prime mover".
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We have assessed the mechanism underlying glial cell-derived neurotrophic factor (GDNF)-induced mechanical hyperalgesia in the gastrocnemius muscle, using patch clamp electrophysiology, in vivo electrophysiology and behavioral studies. Cultured isolectin B4-positive (IB4+) dorsal root ganglion neurons that innervated this muscle were held under current clamp; the majority developed an increase in action potential duration (a factor of increase of 2.29±0.24, compared to 1.13±0.17 in control, P<0.01) in response to GDNF (200 ng/ml) by 15 min after application. They also demonstrated a depolarization of resting membrane potential, but without significant changes in rheobase, action potential peak, or after-hyperpolarization. ⋯ This was observed in the absence of changes in the mechanical threshold. Finally, injection of iberiotoxin into the gastrocnemius muscle produced dose-dependent mechanical hyperalgesia. These data support the suggestion that GDNF induces nociceptor sensitization and mechanical hyperalgesia, at least in part, by inhibiting BK current in IB4+ nociceptors.
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The pyramidal neurons in the hippocampus are extremely neuroplastic, and the complexity of dendritic branches can be dynamically altered in response to a variety of stimuli, including learning and stress. Recently, the teneurin family of proteins has emerged as an interneuronal and extracellular matrix signaling system that plays a significant role in brain development and neuronal communication. Encoded on the last exon of the teneurin genes is a new family of bioactive peptides termed the teneurin C-terminal-associated peptides (TCAPs). ⋯ We postulate that the TCAP-1 region of teneurin-1 has a direct action on the cytoskeletal reorganization that precedes neurite and process development in hippocampal neurons. Our data provides novel evidence that functionally links the teneurin and dystroglycan systems and provides new insight into the molecular mechanisms by which TCAP-1 regulates cytoskeletal dynamics in hippocampal neurons. The TCAP-dystroglycan system may represent a novel mechanism associated with the regulation of hippocampal-function.
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The generation of the most abundant neurons of the cerebellum, the granule cells, relies on a balance between clonal expansion and apoptosis during the first 10 days after birth in the external germinal layer (EGL). The amino acid glutamate controls such critical phases of cell development in other systems through specific receptors such as metabotropic glutamate receptor 5 (mGlu(5)R). However, the function of mGlu(5)Rs on the proliferation and survival of granule cell precursors (GCPs) remains elusive. ⋯ Furthermore, similar treatments led to a significant 70% decrease in the number of apoptotic GCPs in the EGL as determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. In contrast, in vivo treatment with the mGlu(5)R agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) resulted in a ∼60% increase in the number of TUNEL-labeled GCPs compared to control. These findings identify a unique role for glutamate acting at mGlu(5)Rs as a functional switch regulating GCP survival in the EGL, thus controlling the total number of cerebellar granule cells produced.
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Little is known about the projections from the orofacial areas of the secondary somatosensory cortex (S2) to the pons and medulla including the second-order somatosensory neuron pools. To address this in rats, we first examined the distribution of S2 neurons projecting to the trigeminal principal nucleus (Vp) or oral subnucleus (Vo) of the trigeminal sensory nuclear complex (TSNC) after injections of a retrograde tracer, Fluorogold (FG), into five regions in the Vp/Vo which were responsive to stimulation of trigeminal nerves innervating the orofacial tissues. A large number of FG-labeled neurons were found with a somatotopic arrangement in the dorsal areas of S2 (orofacial S2 area). ⋯ The projections to the TSNC showed somatotopic arrangements in dorsoventral, superficial-deep and rostrocaudal directions. The somatotopic arrangements in the Vp/Vo closely matched those of the electrophysiologically defined central projection sites of the orofacial trigeminal afferents in the TSNC. The present results suggest that the orofacial S2 projects selectively to certain rostrocaudal levels of the contralateral TSNC, and the projections may allow the orofacial S2 to accurately modulate orofacial somatosensory transmission to higher brain centers including the orofacial S2 itself.