Neuroscience
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Angiotensin II (Ang II) type 1 (AT1) receptors are prevalent in the sensory vagal complex including the nucleus tractus solitarii (NTS) and area postrema, each of which has been implicated in the central cardiovascular effects produced by Ang II. In rodents, these actions prominently involve the AT1A receptor. Thus, we examined the electron microscopic dual immunolabeling of antisera recognizing the AT1A receptor and Ang II to determine interactive sites in the sensory vagal complex of rat brain. ⋯ In the area postrema, AT1A receptor labeling also was detected in many non-neuronal cells including glia, capillary endothelial cells and perivascular fibroblasts that were less prevalent in the NTS. We conclude that in the rat sensory vagal complex, AT1A receptors are strategically positioned for involvement in modulation of the postsynaptic excitability and intracrine hormone-like effects of Ang II. In addition, these receptors have distributions consistent with diverse roles in regulation of transmitter release, regional blood flow and/or vascular permeability.
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Comparative Study
In vivo evidence for an activity-independent maturation of AMPA/NMDA signaling in the developing hippocampus.
Correlated pre- and postsynaptic activity is thought to promote maturation of excitatory synapses in the developing brain by directing AMPA receptors to pure NMDA synapses. However, this hypothesis has not been tested in vivo. Here, we have performed such test by inhibiting correlated neural activity in vivo using a single injection of tetanus toxin into the rat hippocampal CA1 area at postnatal day 1. ⋯ This activity deprivation led to a growth retardation of CA1 pyramidal neurons and to markedly faster decay kinetics of NMDA sPCSs. However, it did not alter the relationship between AMPA and NMDA sPSCs with respect to either their frequency or amplitude. Thus, although critical for certain aspects of neuronal development, correlated neural activity in the neonatal hippocampus does not seem to promote incorporation of AMPA receptors at pure NMDA synapses.
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Converging evidence in schizophrenia suggests prefrontal cortical neuronal deficits that correlate with exaggerated subcortical dopamine (DA) functions: Excitotoxic lesion of the ventral hippocampus (VH) in neonatal rats is widely considered a putative animal model of schizophrenia as they lead to characteristic post-pubertal emergence of behavioral and cognitive abnormalities suggesting a developmental change in the neural circuits comprising the prefrontal cortex (PFC) and subcortical DA. Nerve growth factor inducible-B (NGFI-B, also known as Nur77), an orphan nuclear receptor and transcriptional regulator, is constitutively expressed in the target structures of DA pathways. It acts as an immediate early gene with rapid modulation of its mRNA expression by stress, DA and antipsychotic drugs. ⋯ Amphetamine treatment increased the expression of NGFI-B mRNA in the mPFC, CC, striatum and NAcc in both control and lesioned animals of both ages. Interestingly, however, striatal and NAcc regions of lesioned rats showed a significantly greater effect of amphetamine at PD56. The data suggest that nVH lesions lead to delayed changes in PFC gene expression along with functional DAergic hyperactivity in subcortical regions.
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Comparative Study
Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation in female prairie voles.
Although oxytocin (OT) and dopamine (DA) have been implicated in pair bond formation in monogamous prairie voles (Microtus ochrogaster), the nature of potential interactions between these two neurochemical systems and the brain circuits important for such interactions in the regulation of pair bonding have not been explored. Here, we demonstrated that access to both OT and DA D2-type receptors is necessary for pair bond formation, as blockade of either type of receptor prevented partner preferences induced by OT or a D2-type agonist. ⋯ In NAcc, blockade of OT receptors prevented partner preferences induced by a D2-type agonist whereas blockade of D2-type, but not D1-type, DA receptors blocked OT-induced partner preferences. Together, our data suggest that concurrent activation of OT and DA D2-type receptors in NAcc is essential for pair bond formation in female prairie voles.
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Comparative Study
The fragile X mental retardation protein binds and regulates a novel class of mRNAs containing U rich target sequences.
Fragile X syndrome is a common form of inherited mental retardation caused by the absence of the fragile X mental retardation protein (FMRP). It has been hypothesized that FMRP is involved in the processing and/or translation of mRNAs. Human and mouse target-mRNAs, containing purine quartets, have previously been identified. ⋯ Many of the proteins encoded by the identified FMRP targets have been implicated in neuroplasticity. Steady state levels of target-mRNAs were unchanged in the brain of fragile X mice. However, levels of two target-encoded proteins, an L-type calcium channel subunit and MAP1B, were downregulated in specific brain regions suggesting a defect in the expression of target-encoded proteins in fragile X syndrome.