The Journal of comparative neurology
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Rats develop hyperalgesia and allodynia in the hind paw after L5 spinal nerve ligation. Phosphorylated extracellular regulated kinase (pERK) was used as a pain marker to investigate the potential role of adjacent uninjured L4 nerve in the development of heat hyperalgesia after L5 nerve injury. Left L5 nerve was ligated and sectioned in rats. ⋯ There was a linear increase in pERK immunoreactivity on both sides with an increase in temperature. Importantly, the number of positive pERK neurons was significantly higher in the ipsilateral side of L4 spinal segment, which receives innervation from uninjured L4 nerve, compared with the contralateral control side, which receives both uninjured L4 and L5 spinal nerves. The data demonstrate that the uninjured L4 nerve plays an important role in the development of heat hyperalgesia at the spinal cord level after L5 nerve injury.
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Odor information relayed by olfactory bulb projection neurons, mitral and tufted cells (M/T), is modulated by pairs of reciprocal dendrodendritic synaptic circuits in the external plexiform layer (EPL). Interneurons, which are accounted for largely by granule cells, receive depolarizing input from M/T dendrites and in turn inhibit current spread in M/T dendrites via hyperpolarizing reciprocal dendrodendritic synapses. Because the location of dendrodendritic synapses may significantly affect the cascade of odor information, we assessed synaptic properties and density within sublaminae of the EPL and along the length of M/T secondary dendrites. ⋯ Synaptic density, expressed as a function of surface area, increases distal to the cell body. Furthermore, the distributions of gephyrin-IR puncta are heterogeneous and appear as clusters along the length of the M/T dendrites. Consistent with computational models, our data suggest that temporal coding in M/T cells is achieved by precisely located inhibitory input and that distance from the soma is compensated for by an increase in synaptic density.
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Perineuronal nets (PNNs) are closely associated with parvalbumin-positive (PV+) neurons, and play a major role in controlling developmental neural plasticity. Considering the recent advances in classification of PV+ neurons, here we aimed to clarify whether PNNs might be associated with specific subclasses of PV+ neurons in the hippocampus. In this study, we labeled PNNs by Wisteria floribunda agglutinin (WFA), and classified PV+ neurons based on the combination of cellular location, molecular expression (neuropeptide Y [NPY], somatostatin [SOM], special AT-rich sequence-binding protein-1 [SATB1]), and retrograde tracing through stereotaxic injection of Fluoro-Gold (FG) into the medial septum. ⋯ The vast majority (over 90%) of putative PV+ basket cells were surrounded by PNNs, while only a minor population (less than 10%) of putative PV+ axo-axonic, O-LM, and H-S cells were enwrapped with PNNs. The ratios of formation of PNNs around putative PV+ bistratified cells were intermediate (25-50%). These findings indicate that PNNs may be specifically associated with PV+ basket cells, and also provide a key to understand the functional significance of PNNs and PV+ neurons in the hippocampus.
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Growth hormone secretagogue receptor (GHSR) 1a is the only molecularly identified receptor for ghrelin, mediating ghrelin-related effects on eating, body weight, and blood glucose control, among others. The expression pattern of GHSR within the brain has been assessed previously by several neuroanatomical techniques. However, inherent limitations to these techniques and the lack of reliable anti-GHSR antibodies and reporter rodent models that identify GHSR-containing neurons have prevented a more comprehensive functional characterization of ghrelin-responsive neurons. ⋯ In contrast, eGFP expression was low in several midbrain regions and in several hypothalamic nuclei, particularly the arcuate nucleus, where robust GHSR mRNA expression has been well-characterized. eGFP expression in several brainstem nuclei showed high to moderate degrees of colocalization with GHSR mRNA labeling. Further quantitative PCR and electrophysiological analyses of eGFP-labeled hippocampal cells confirmed faithful expression of eGFP within GHSR-containing, ghrelin-responsive neurons. In summary, the GHSR-eGFP reporter mouse model may be a useful tool for studying GHSR function, particularly within the brainstem and hippocampus; however, it underrepresents GHSR expression in nuclei within the hypothalamus and midbrain.
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Dendritic spine loss is observed in many psychiatric disorders, including schizophrenia, and likely contributes to the altered sense of reality, disruption of working memory, and attention deficits that characterize these disorders. ErbB4, a member of the EGF family of receptor tyrosine kinases, is genetically associated with schizophrenia, suggesting that alterations in ErbB4 function contribute to the disease pathology. Additionally, ErbB4 functions in synaptic plasticity, leading us to hypothesize that disruption of ErbB4 signaling may affect dendritic spine development. ⋯ We find that ErbB4 localizes to dendritic spines of excitatory neurons in cortical neuronal cultures and is present in synaptic plasma membrane preparations. Finally, we demonstrate that selective ablation of ErbB4 from excitatory neurons leads to a decrease in the proportion of mature spines and an overall reduction in dendritic spine density in the prefrontal cortex of weanling (P21) mice that persists at 2 months of age. These results suggest that ErbB4 signaling in excitatory pyramidal cells is critical for the proper formation and maintenance of dendritic spines in excitatory pyramidal cells.