Neuroscience
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The hypothalamic nonapeptide oxytocin (OT) has an established role as a circulating hormone but can also act as a neurotransmitter and as a neuromodulator by interacting with its central OT receptor (OTR). To understand the role of the OTR in the mouse brain we investigated the expression of the OTR gene at the cellular level. We targeted the lacZ reporter gene to the OTR gene locus downstream of the endogenous OTR regulatory elements. ⋯ By mapping the distribution of OTR gene expression, depicted through histochemical detection of beta-galactosidase, we were able to identify single OTR gene expressing neurons and small neuron clusters that would have remained undetected by conventional approaches. These novel sites of OTR gene expression suggest additional functions of the oxytocinergic system in the mouse. These results lay the foundation for future investigation into the neural role of the OTR and provide a useful model for further study of oxytocin functions in the mouse.
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There are many evidences implicating glutamatergic toxicity as a contributory factor in the selective neuronal injury occurring in amyotrophic lateral sclerosis (ALS). This neurodegenerative disorder is characterized by the progressive loss of motor neurons, whose pathogenesis is thought to involve Ca(2+) influx mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors (AMPARs). ⋯ Compared with those expressed in motor neurons carrying the human wild type gene, AMPAR-gated channels expressed in motor neurons carrying the human mutant gene exhibited modified permeability, altered agonist cooperativity between the sites involved in the process of channel opening and were responsible for slower spontaneous synaptic events. These observations demonstrate that the SOD1(G93A) mutation induces changes in AMPAR functions which may underlie the increased vulnerability of motor neurons to glutamatergic excitotoxicity in ALS.
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Comparative Study
Inhibitory cotransmission or after-hyperpolarizing potentials can regulate firing in recurrent networks with excitatory metabotropic transmission.
Recurrent networks of neurons communicating via excitatory connections are common in the nervous system. In the absence of mechanisms to control firing (collectively termed negative feedback), these networks are likely to be bistable and unable to meaningfully encode input signals. In most recurrent circuits, negative feedback is provided by a specialized subpopulation of interneurons, but such neurons are absent from some systems, which therefore require other forms of negative feedback. ⋯ In addition, simulation revealed that neurons in networks with inhibitory contransmission fired in erratic bursts, a phenomenon observed in neurons in unparalysed tissue. Thus, either inhibitory contransmission or AHPs, or both, can allow recurrent networks of AH/Dogiel type II neurons to encode ongoing inputs in a biologically useful way. These neurons appear to be intrinsic primary afferent neurons (IPANs), which implies that the IPANs in a region act in a coordinated fashion.
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Emotional development is indisputably one of the cornerstones of personality development during infancy. According to the differential emotions theory (DET), primary emotions are constituted of three distinct components: the neural-evaluative, the expressive, and the experiential. The DET further assumes that these three components are biologically based and functional nearly from birth. ⋯ These results are compatible with those of previous functional neuroimaging studies of sadness in adults. They suggest that the neural substrate underlying the subjective experience of sadness is comparable in children and adults. Such a similitude provides empirical support to the DET assumption that the neural substrate of primary emotions is biologically based.
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Comparative Study
Association of gephyrin and glycine receptors in the human brainstem and spinal cord: an immunohistochemical analysis.
Gephyrin is a postsynaptic clustering molecule that forms a protein scaffold to anchor inhibitory neurotransmitter receptors at the postsynaptic membrane of neurons. Gephyrin was first identified as a protein component of the glycine receptor complex and is also colocalized with several GABAA receptor subunits in rodent brain. We have studied the distribution of gephyrin and glycine receptor subunits in the human brainstem and spinal cord using immunohistochemistry at light and confocal laser scanning microscopy levels. ⋯ Colocalization of immunoreactivities for gephyrin and glycine receptor subunits was detected in the dorsal and ventral horns of the spinal cord, the hypoglossal nucleus and the medial vestibular nucleus of the medulla. The results clearly establish that gephyrin is ubiquitously distributed and is colocalized, with a large proportion of glycine receptor subunits in the human brainstem and spinal cord. We therefore suggest that gephyrin functions as a clustering molecule for major subtypes of glycine receptors in the human CNS.