Brain research
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Increased output from the subthalamic nucleus (STN) following chronic dopamine depletion has been linked to the rigidity and tremor seen in Parkinson's disease (PD). We used extracellular microelectrode recordings from rat brain slices to investigate effects of dopamine on STN neurons. In brain slices prepared from rats that received unilateral 6-hydroxydopamine (6-OHDA) treatment, the spontaneous firing rate of STN neurons was reduced by 63%, and the firing pattern was more irregular, compared to STN neurons from normal rats. ⋯ This excitatory effect of dopamine was mimicked by a D2 receptor agonist (quinpirole), and was reduced by the D2 antagonists haloperidol, clozapine and sulpiride. Antagonists of the D1 receptor (SCH-23390) and ionotropic glutamatergic receptors (CNQX and AP5) could not block the effect of dopamine on firing rate. These results suggest that dopamine exerts a direct excitatory influence on STN neurons via the activation of D2-like receptors.
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Neurokinin 1 receptor (NK1R) internalization in dorsal horn neurons is important for intracellular signaling in nociception. Since the rates of NK1R internalization and recycling vary substantially, particularly between cultured and native cells, it is imperative to characterize them in dorsal horn neurons. When rat spinal cord slices were incubated at 35 degrees C with 1 microM substance P (SP), NK1Rs in lamina I neurons internalized rapidly following apparent exponential association kinetics (half-life=71 s). ⋯ NK1R internalization and recycling also occurred in lamina I dendrites. NK1R-containing endosomes in dendrites did not migrate to the cytoplasm. These results show that NK1R internalization and recycling are considerably faster in dorsal horn neurons than in cultured cells, and that most NK1Rs in dorsal horn neurons are internalized when NK1R-mediated hyperalgesia is more severe.
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Previous studies have observed that pial artery dilation to activators of the ATP sensitive K (K(ATP)) and calcium sensitive K (K(ca)) channel was blunted following fluid percussion brain injury (FPI) in the piglet. In recent studies in the rat, protein tyrosine kinase (PTK) activation was observed to contribute to K(ATP) channel impairment after FPI, but such a role in K(ca) channel impairment was unclear. ⋯ Cromakalim- and NS1619-induced pial dilation was also partially restored after FPI by pretreatment with the MAPK inhibitors U0126 (10(-6) M) and PD98059 (10(-5) M) (12+/-1 and 21+/-1%, sham control; 2+/-1 and 4+/-1%, FPI; and 6+/-1 and 10+/-2%, FPI-U0126 pretreated for NS1619 10(-8), 10(-6) M, respectively). These data suggest that PTK and MAPK activation contribute to K(ATP) and K(ca) channel impairment following FPI.
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There are discrete subpopulations of GABAergic interneurons in the basolateral amygdala (ABL) that contain particular neuropeptides or calcium-binding proteins (calbindin-D28k, parvalbumin (PV), or calretinin). The present study employed a dual-labeling immunofluorescence technique combined with confocal laser scanning microscopy to investigate the neurochemical characteristics of the interneuronal subpopulation containing somatostatin (SOM). The great majority of SOM+ neurons in the ABL exhibited GABA immunoreactivity (66-82% depending on the nucleus). ⋯ In the basolateral nucleus more than 90% of SOM+ neurons also exhibited CB immunoreactivity, whereas in the lateral nucleus about two-thirds of SOM+ neurons contained significant levels of CB. These SOM/CB neurons constituted about one quarter of the CB+ population in the basolateral nucleus and about one third of the CB+ population in the lateral nucleus. These results, in conjunction with the findings of previous studies, indicate that there are at least three major subpopulations of GABAergic interneurons in the ABL: (i) SOM+ neurons (most of which also contain CB and/or neuropeptide Y); (ii) PV+ neurons (most of which also contain CB); and (iii) CR+ neurons (most of which also contain vasoactive intestinal polypeptide).