Neuroscience
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Reaching for food, or skilled reaching, is used as a test of basal ganglia function in preclinical studies as well as studies of human neurological conditions. Although changes in the end-point measure of success document the effects of neurotoxic cellular damage to the caudate-putamen and its treatment in rodents, there has been no examination of the cause of change in success after neurotoxic lesions of the striatum. This objective was addressed in the present study, in which rats trained to reach for single food pellets with one forelimb, received contralateral quinolinic acid or ibotenic acid lesions of the medial and lateral caudate-putamen. ⋯ After recovery of the withdrawal movement, the rats displayed chronic qualitative impairments in the rotatory movements of aiming, pronating, and supinating the forepaw. Medial quinolinic lesions improved success relative to control rats and did not change qualitative aspects of limb movement. The acute dissociation between transport and withdrawal, the chronic qualitative changes in movement elements, and the differential effect of medial and lateral injury on success, support a complex contribution of the caudate-putamen to skilled reaching that includes sensorimotor neglect, and quantitative and qualitative motoric changes.
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The striatum is thought to be an essential region for integrating diverse information in the brain. Rapid inhibitory gating (IG) of sensory input is most likely an early factor necessary for appropriate integration to be completed. Gating is currently evaluated in clinical settings and is dramatically altered in a variety of psychiatric illnesses. ⋯ Gating was strengthened (Tamp/Camp ratios approaching 0) following acute stress (saline injection) at both the single unit and LFP level due to the reduction in the response to the second tone. Alterations in sensory responding reflected by changes in the neural response to the initial tone were primarily observed following long-term internal state deviation (food deprivation) and during general locomotion. Overall, our results support local IG by single neurons in striatum but also suggest that rapid inhibition is not the dominant activation profile observed in other brain regions.
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We previously demonstrated that peripherally located N-methyl-D-aspartic acid (NMDA) receptors contribute to acute muscle nociception and the development of chronic muscular hyperalgesia. In the present study, we investigated the potential role of peripheral group I metabotropic glutamate receptors (mGluRs 1/5) in the development of muscular hypersensitivity to mechanical stimulation, and attempted to elucidate intracellular signaling mechanisms associated with the mGluR activation in male Sprague-Dawley rats. First, our Western blot analyses revealed that mGluR 5 protein, but not mGluR 1 protein, is reliably detected in trigeminal ganglia and the masseter nerve. ⋯ Moreover, the DHPG-induced mechanical hypersensitivity was significantly blocked by inhibiting either the alpha or epsilon isoform of protein kinase C (PKC). Collectively, these data provide evidence that peripherally located mGluR 5 may play an important role in the development of masseter hypersensitivity, and that PKC activation is required for the modulatory effect of peripheral mGluR 5 in the craniofacial muscle tissue. Thus, selective targeting of peripheral mGluR 5 and PKCalpha, as well as PKCepsilon, might serve as an effective therapeutic strategy in the management of chronic muscle pain conditions, such as temporomandibular disorders.
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Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that contributes to both neuronal death and survival under stress conditions. PARP-1 is the most abundant of several PARP family members, accounting for more than 85% of nuclear PARP activity, and is present in all nucleated cells of multicellular animals. ⋯ PARP-1 activation is thereby a key mediator of neuronal death during excitotoxicity, ischemia, and oxidative stress, and PARP-1 gene deletion or pharmacological inhibition can markedly improve neuronal survival in these settings. PARP-1 activation has also been identified in Alzheimer's disease and in experimental allergic encephalitis, but the role of PARP-1 in these disorders remains to be established.
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Oligodendrocytes are crucial to the function of the mammalian brain: they increase the action potential conduction speed for a given axon diameter and thus facilitate the rapid flow of information between different brain areas. The proliferation and differentiation of developing oligodendrocytes, and their myelination of axons, are partly controlled by neurotransmitters. ⋯ Mutations in oligodendrocyte neurotransmitter receptors or their interacting proteins may cause defects in CNS function. Here we review the roles of neurotransmitter receptors in the normal function, and malfunction in pathological conditions, of oligodendrocytes.