PubMed · 5121771
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V K Bhargava, B S Meldrum. 1971. Cholinergic cortical evoked potentials.. https://pubmed.ncbi.nlm.nih.gov/5121771/
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Cholinergic neurons in the basal forebrain are the focus of considerable interest because they are severely affected in Alzheimer's disease. However, both cholinergic and noncholinergic neurons are intermingled in this region. The goal of the present study was to characterize the morphology and in vivo electrophysiology of noncholinergic basal forebrain neurons. Neurons in the ventral pallidum and substantia innominata were recorded extracellularly, labeled juxtacellularly with biocytin and characterized for the presence of choline acetyltransferase immunoreactivity. Two types of ventral pallidal cells were observed. Type I ventral pallidal neurons had axons that rarely branched near the cell body and tended to have smaller somata and lower spontaneous firing rates than did type II ventral pallidal neurons, which displayed extensive local axonal arborizations. Subtypes of substantia innominata neurons could not be distinguished based on axonal morphology. These noncholineregic neurons exhibited local axon arborizations along a continuum that varied from no local collaterals to quite extensive arbors. Substantia innominata neurons had lower spontaneous firing rates, more variable interspike intervals, and different spontaneous firing patterns than did type II ventral pallidal neurons and could be antidromically activated from cortex or substantia nigra, indicating that they were projection neurons. Ventral pallidal neurons resemble, both morphologically and electrophysiologically, previously described neurons in the globus pallidus, whereas the substantia innominata neurons bore similarities to isodendritic neurons of the reticular formation. These results demonstrate the heterogeneous nature of noncholinergic neurons in the basal forebrain.
The Rab3 proteins are monomeric GTP-binding proteins associated with secretory vesicles. In their active GTP-bound state, Rab3 proteins are involved in the regulation of hormone secretion and neurotransmitter release. This action is thought to involve specific effectors, including two Ca2+-binding proteins, Rabphilin and Rim. Rab3 acts late in the exocytotic process, in a cell domain in which the intracellular Ca2+ concentration is susceptible to rapid changes. Therefore, we examined the possible Ca2+-dependency of the regulatory action of GTP-bound Rab3 and wild-type Rab3 on neuroexocytosis at identified cholinergic synapses in Aplysia californica. The effects of recombinant GTPase-deficient Aplysia-Rab3 (apRab3-Q80L) or wild-type apRab3 were studied on evoked acetylcholine release. Intraneuronal application of apRab3-Q80L in identified neurons of the buccal ganglion of Aplysia led to inhibition of neurotransmission; wild-type apRab3 was less effective. Intracellular chelation of Ca2+ ions by EGTA greatly potentiated the inhibitory action of apRab3-Q80L. Train and paired-pulse facilitation, two Ca2+-dependent forms of short-term plasticity induced by a rise in intraterminal Ca2+ concentration, were increased after injection of apRab3-Q80L. This result suggests that the inhibition exerted by GTP-bound Rab3 on neuroexocytosis is reduced during transient augmentations of intracellular Ca2+ concentration. Therefore, a Ca2+-dependent modulation of GTP-bound Rab3 function may contribute to short-term plasticity.
1. The types of voltage-dependent calcium channels (VDCCs) present in the cholinergic terminals isolated from the electric organ of the ray, Narke japonica, were characterized on the basis of their pharmacological sensitivity to specific antagonists. Inhibition of these channel types by autoantibodies from patients with the Lambert-Eaton syndrome (LES) was then studied to determine the specificity of the pathogenic IgG. 2. In normal untreated synaptosomal preparations, maximal doses of N- and P and/or Q-type Ca2+ channel antagonists, omega-conotoxin GVIA and omega-agatoxin IVA, inhibited depolarization-evoked ACh release by 47 % and 43 %, respectively. Calciseptine, an L-type VDCC antagonist, caused a 20 % reduction in the release. This indicates that the exocytotic release process is predominantly mediated by N- and P/Q-type VDCCs. 3. LES IgG or sera caused an inhibition of ACh release by 39-45 % in comparison with the control antibody-treated preparations. The ionomycin-induced ACh release, however, was not altered by the antibodies. Additionally, the same LES antibodies inhibited whole-cell calcium currents (ICa) in bovine adrenal chromaffin cells. Thus, the pathogenic antibodies exert their action on VDCCs present in the synaptosomes. 4. The efficacy of three Ca2+ channel antagonists in blocking ACh release was determined in preparations pretreated with LES IgG. omega-Agatoxin IVA produced only an additional 3-5 % reduction in release beyond that obtained with LES antibodies. Despite the pretreatment with LES IgG, omega-conotoxin GVIA and calciseptine inhibited the release to nearly their control levels. 5. These results indicate that LES antibodies mainly downregulate P/Q-type Ca2+ channels which contribute to presynaptic transmitter release from the cholinergic nerve terminals of electric organ. 6. The present findings are consistent with the hypothesis that P/Q-type VDCCs at the neuromuscular junction are the target of LES antibodies and that their inhibition by the antibodies produces the characteristic neuromuscular defect in this disease.