Electrical stimulation (ten pulses of 0.5 ms, 10 V applied over 10 s at 10 Hz, 140 microA) delivered bilaterally to the prefrontal cortex or the parafascicular thalamic nucleus of freely moving rats facilitated acetylcholine release in dorsal striata, assessed by trans-striatal microdialysis. The facilitatory effects were blocked by coperfusion with 5 microM tetrodotoxin, suggesting that the release was of neuronal origin. The response of the striatal cholinergic neurons to prefrontal cortical stimulation was short-lived and required a longer period of stimulation (20 min) that the response to thalamic stimulation (4 min) to reach maximal effect. The alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate glutamatergic receptor antagonist 6,7-dinitroquinoxaline-2,3-dione [DNQX; 12 nmol per side, intracerebroventricularly (i.c.v.)] and the AMPA antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (NBQX; 12 nmol per side, i.c.v. or 12.8 microM infused into the striatum), but not the NMDA-type receptor antagonist MK-801 (0.2 mg/kg, i.p.), abolished the facilitatory effect on striatal acetylcholine release evoked by stimulation of the prefrontal cortex. By contrast, DNQX or NBQX did not prevent the increase in striatal acetylcholine release evoked by parafascicular nucleus stimulation, but MK-801, in accordance with previous results, did so. MK-801 by itself lowered striatal acetylcholine output while DNQX and NBQX did not. The results provide in vivo evidence that the cerebral cortex facilitates cholinergic activity in the dorsal striatum apparently through the non-tonic activation of AMPA-type glutamatergic receptors while the parafascicular nucleus does this through tonic activation of NMDA receptors. Both glutamate receptor types are probably located in the striatum. The overall results suggest that the two pathways operate independently to regulate striatal cholinergic activity through distinct mechanisms.
Using microdialysis and a sensitive RIA, we have studied the in vivo release of the neuropeptide galanin (GAL) from the ventral hippocampus of freely moving rats.The spontaneous outflow of GAL-like immiunoreactivity (GAL-LI) (1.8 ± 0.3 fmol per ml per 20 min) was dependent on the presence of extraceliular Ca2+ and was inhibited by tetrodotoxin. Evoked release induced by infusion of KCI (60 mM) or veratridine (148 FM) was also Ca2+-dependent and sensitive to tetrodotoxin. Electrical stimulation of the ventral limb of the diagonal band nuclei induced a frequency-dependent Hz) and tetrodotoxin-sensitive overflow of GAL-LI in the hippocampus. In vitro GAL-LI release (1.0 ± 0.02 fmol per ml per 5 min), studied in slices of rat ventral hippocampus, was also Ca2+-dependent and was increased in a concentrationdependent manner by KC1 depolarization. This study demonstrates the release of the neuropeptide GAL in the rat central nervous system. The in vivo release is related to the activity of the cholinergic GAL-LI-containing cells in the septal diagonal band nuclei. The results are discussed in relation to the coexistence of GAL and acetylcholine within the septal/diagonal band complex.Galanin (GAL) is a neuropeptide with widespread distribution in the endocrine and peripheral and central nervous systems (1-3) where it coexists with several classical neurotransmitters and peptides (3, 4). It appears to be involved in a variety of physiological processes including hormone secretion, neuronal activity, and smooth muscle contractility (4, 5).Recent studies have reported on the effects of GAL in memory-related behaviors. The peptide impairs acquisition in the Morris swim maze (6) and in the delayed alternation T test (7), while the chimeric peptide GAL receptor antagonist M35[galanin-(1-13)-bradykinin (2-9)] improved performance in the Morris swim test (8). These effects are believed to be exerted through interactions with the cholinergic forebrain neurons originating in the septal diagonal band nuclei and projecting to the hippocampus. Immunohistochemical and in situ hybridization studies have shown that GAL is synthesized and stored in the septal hippocampal cholinergic neurons in rodents and monkeys (9, 10). Actually, GAL is the only peptide known to coexist with acetylcholine (AcCho) in the forebrain neurons. GAL receptor autoradiography in combination with septal lesions indicates that in the ventral hippocampus of the rat these receptors are postsynaptic or are localized on the cholinergic nerve terminals (9).Exogenous GAL inhibits the evoked release of AcCho both in vivo and in vitro and several GAL receptor antagonists reverse this effect (11-13). It also exerts an inhibitory effect on the postsynaptic muscarinic stimulation of inositol phospholipid production in the ventral hippocampus (14). On the other hand, the contribution ofendogenous GAL to these effects has still not been tested. The presence of GAL in neurons, as shown by immunocytochemistry, cannot be taken as proof that the peptide is indeed relea...
Electrical stimulation of the parafascicular but not the ventrolateral or dorsomedial thalamic nucleus (ten 0.5 ms, 10 V pulses, 140 microA) of freely moving rats induced a frequency-dependent (2.5, 5, 10 and 20 Hz) increase in the extracellular acetylcholine (ACh) content of the dorsal striatum, assessed by trans-striatal microdialysis. The time-dependent effect of 10 Hz stimulation was studied. The peak increase, 39% above baseline, was attained during 4 min of stimulation. This was blocked by coperfusion with 5 microM tetrodotoxin, indicating that the release we measured represents a physiological process. The facilitatory effect of parafascicular nucleus stimulation does not appear to be associated with indirect action through the cerebral frontal cortex because acute lesion of the excitatory corticostriatal afferents, which by itself reduced basal ACh release by 40%, did not modify the effect of 10 Hz stimulation. The possible involvement of the fasciculus retroflexus in the facilitation of ACh release was also ruled out. The non-competitive NMDA-type receptor antagonist MK-801, applied by reversed dialysis (30 microM) or systemically injected (0.2 mg/kg), significantly reduced the basal ACh output and prevented the tetanus-evoked increase in ACh release. The results provide in vivo evidence that the activity of the cholinergic neurons in the dorsal striatum is trans-synaptically modulated by parafascicular nucleus excitatory afferents through activation of the NMDA subtype of glutamate receptors that is probably located in the striatum.
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