Neuroscience
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Comparative Study
Stereological estimation of Purkinje neuron number in C57BL/6 mice and its relation to associative learning.
Cerebellar Purkinje neurons are among the most vulnerable neurons in the CNS. Impairment in Purkinje neurons has consequences for cerebellar cortical-dependent forms of behavior. The primary aim of this study was to evaluate Purkinje neuron number over the lifespan of C57BL/6 mice. ⋯ Eliminating the hearing-impaired 18- and 24-month-old mice from the analysis, the correlation between Purkinje neuron number and rate of conditioning was -0.435 (P=0.053) in 15 younger mice aged 4-12 months. Purkinje neurons are one of the few types of neurons showing significant age-associated loss. Results indicate that individual variation in Purkinje neuron number is related to eyeblink conditioning in young organisms suggesting that reserves of neuron numbers against which individuals draw are defined early in life.
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Comparative Study
Inflammation increases the excitability of masseter muscle afferents.
Temporomandibular disorder is a major health problem associated with chronic orofacial pain in the masticatory muscles and/or temporomandibular joint. Evidence suggests that changes in primary afferents innervating the muscles of mastication may contribute to temporomandibular disorder. However, there has been little systematic study of the mechanisms controlling the excitability of these muscle afferents, nor their response to inflammation. ⋯ These changes in excitability and action potential waveform were associated with significant shifts in the voltage-dependence of activation and steady-state availability of voltage-gated K(+) current as well as significant decreases in the density of voltage-gated K(+) current subject to steady-state inactivation. These data suggest that K(+) channel subtypes may provide novel targets for the treatment of pain arising from inflamed muscle. These results also support the hypothesis that the underlying mechanisms of pain arising from specific regions of the body are unique suggesting that it may be possible, if not necessary to treat pain originating from different parts of the body with specific therapeutic interventions.
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Comparative Study
The tyrosine receptor kinase B ligand, neurotrophin-4, is not required for either epileptogenesis or tyrosine receptor kinase B activation in the kindling model.
The kindling model of epilepsy is a form of neuronal plasticity induced by repeated induction of pathological activity in the form of focal seizures. A causal role for the neurotrophin receptor, tyrosine receptor kinase B, in epileptogenesis is supported by multiple studies of the kindling model. Not only is tyrosine receptor kinase B required for epileptogenesis in this model but enhanced activation of tyrosine receptor kinase B has been identified in the hippocampus in multiple models of limbic epileptogenesis. ⋯ No differences were found between +/+ and -/- mice with respect to any facet of the development or persistence of kindling. Despite the absence of NT4, activation of the tyrosine receptor kinase B receptor in the mossy fiber pathway as assessed by phospho-trk immunohistochemistry was equivalent to that of +/+ mice. Together these findings demonstrate that NT4 is not required for limbic epileptogenesis nor is it required for activation of tyrosine receptor kinase B in hippocampus during limbic epileptogenesis.
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Comparative Study
Atp2b2, encoding plasma membrane Ca2+-ATPase type 2, (PMCA2) exhibits tissue-specific first exon usage in hair cells, neurons, and mammary glands of mice.
Atp2b2 encodes the plasma membrane Ca(2+)-ATPase type 2 (PMCA2) expressed in various tissues, including stereocilia of cochlear and vestibular hair cells, cerebellar Purkinje cells, and lactating mammary epithelia. Mutations of the gene lead to deafness, ataxia, and reduced Ca(2+) levels in milk. Heterozygous mutants also have abnormal hearing, suggesting that precise regulation of Atp2b2 is required for normal function. ⋯ The regions around the mu and delta first exons are highly conserved between rat and mouse, but less so with other species. Our results show that expression of Atp2b2 is highly regulated, using four different transcriptional start regions, two of which are differentially expressed in neuronal tissue. This suggests that unique regulatory mechanisms are used to control Atp2b2 expression in different types of cells.
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Comparative Study
Absence of GABA type A signaling in adult medial habenular neurons.
Neural inhibition in the brain is mainly mediated by ionotropic GABA type A receptors. Apart from the GABA type A receptors, both K(+)-Cl(-) cotransporter isoform 2 and the GABA-synthesizing enzyme, glutamic acid decarboxylase, are essential determinants for GABA type A receptor-mediated inhibition. By using immunofluorescent staining, we observed that K(+)-Cl(-) cotransporter isoform 2, GABA type A receptor beta2/3 subunits and a presynaptically localized glutamic acid decarboxylase isoform, glutamic acid decarboxylase 65, were all absent in adult Sprague-Dawley rat medial habenular nucleus, while immunopositive staining for glutamic acid decarboxylase 67, GABA and GABA type B receptor type 2 subunit were present in the medial habenular nucleus. ⋯ These results support the idea that GABAergic transmission in medial habenular nucleus is probably not mediated by any of the most common GABA type A receptor subtypes. Our data suggest that GABA type B receptor-mediated inhibition may play a role in balancing neuronal excitation in this special region. Further exploration for factors determining medial habenular nucleus neural inhibition will lead to a more complete understanding of control of synaptic balance in the CNS.