Neuroscience
-
Partial injury of the rat sciatic nerve elicits a variety of characteristic chemical, electrophysical and anatomical changes in primary sensory neurons and constitutes a physiologically relevant model of neuropathic pain. To elucidate molecular mechanisms that underlie the physiology of neuropathic pain, we have used messenger RNA differential display to identify genes that exhibit increased ipsilateral expression in L4/5 dorsal root ganglia, following unilateral partial ligation of the rat sciatic nerve. ⋯ Induction of nerve injury-associated kinase expression in dorsal root ganglia in the rat neuropathic pain model was confirmed by quantitative reverse transcription-polymerase chain reaction, and RNA in situ hybridization analysis revealed enhanced levels of nerve injury-associated kinase within neurons. Together, our data implicate nerve injury-associated kinase as a novel upstream component of an intracellular signalling cascade that is up-regulated in dorsal root ganglia neurons in response to sciatic nerve injury.
-
The cornea is innervated by three functional types of neurons: mechanosensory, polymodal and cold-sensitive neurons, all of which are presumed to be nociceptive. To explore if corneal neurons constitute a heterogeneous population according to their electrophysiological properties, intracellular recordings were made in vitro from trigeminal ganglion neurons innervating the cornea of the mouse. Corneal neurons were labelled with FluoroGold applied after a corneal epithelial wound. ⋯ Neurons with a slower action potential showing a hump in the repolarization phase are both corneal Adelta and C polymodal nociceptive neurons, a type of cell in which tetrodotoxin-resistant Na(+) channels have been identified. The possibility is raised that the small population of neurons with a very high input resistance are cold-sensitive neurons. From the present results, we suggest that the electrophysiological properties of primary sensory neurons innervating the cornea are attributable not only to their conduction velocities, but also to the functional characteristics of their peripheral nerve terminals.
-
GABA is one of the most important inhibitory neurotransmitters in the substantia nigra. Functions of GABA are mediated by two major types of GABA receptors, namely the GABA(A) and GABA(B) receptors. Subunits of both the GABA(A) and GABA(B) receptors have been cloned and functional characteristics of the receptors depend on their subunit compositions. ⋯ In addition, triple-labeling experiments revealed that at the single cell level, the tyrosine hydroxylase-positive, i.e. the dopaminergic neurons in the compacta displayed intense immunoreactivity for GABA(B)R1 but not GABA(A)alpha1 receptors. The parvalbumin-positive neurons in the reticulata displayed intense immunoreactivity for GABA(A)alpha1 but not GABA(B)R1 receptors. The present results demonstrate in the same sections that there is a distinct pattern of localization of GABA(B)R1 and GABA(A)alpha1 receptor immunoreactivity in different subpopulations of the rat substantia nigra and provide anatomical evidence for GABA neurotransmission in the subpopulations of nigral neurons.
-
Striatal nicotinic acetylcholine receptors with high affinity for nicotinic agonists are involved with the release of a number of neurotransmitters, including dopamine. Previous findings as to whether these receptors are changed in Parkinson's disease and Alzheimer's disease are inconsistent and no previous investigations have focused on these receptors in dementia with Lewy bodies and schizophrenia, which are also associated with disorders of movement. The present autoradiographic study of striatal [3H]nicotine binding in Alzheimer's and Parkinson's diseases, dementia with Lewy bodies and schizophrenia was conducted with particular reference to the potentially confounding variables of tobacco use and neuroleptic medication. [3H]Nicotine binding in both dorsal and ventral caudate and putamen was significantly reduced in Parkinson's disease (43-67%, n=13), Alzheimer's disease (29-37%, n=13) and dementia with Lewy bodies (50-61%, n=20) compared to age-matched controls (n=42). ⋯ In contrast, striatal [3H]nicotine binding in a group of elderly (56-85 years) chronically medicated individuals with schizophrenia (n=6) was elevated compared with the entire control group (48-78%, n=42) and with a subgroup that had smoked (24-49%, n=8). The changes observed in [3H]nicotine binding are likely to reflect the presence of these receptors on multiple sites within the striatum, which may be differentially modulated in the different diseases. Further study is warranted to explore which nicotinic receptor subunits and which neuronal compartments are involved in the changes in [3H]nicotine binding reported, to aid development of potential nicotinic receptor therapy.
-
Corticotropin releasing factor is a 41 amino acid peptide that is present in afferent systems that project to the cerebellum. In the adult, this peptide modulates the activity of Purkinje cells by enhancing their responsiveness to excitatory amino acids. Two different types of corticotropin releasing factor receptors, designated type 1 and type 2, have been identified. ⋯ Finally, numerous elongated processes within the white matter, which are likely to be axons, also are type 2 immunoreactive. These data indicate that both types of corticotropin releasing factor receptor are present in the mouse cerebellum. However, the unique distribution of the two types of receptor strongly suggests a differential role for corticotropin releasing factor in modulating the activity of neurons, axons and glial cells via cell-specific ligand-receptor interactions.