GABAergic neurons in the rat hippocampal formation: ultrastructure and synaptic relationships with catecholaminergic terminals

Abstract

Numerous studies indicate that gamma-aminobutyric acid (GABA) can either hyperpolarize or depolarize hippocampal pyramidal and granule cells. While the inhibitory action of GABA may occur directly on these cells, the excitatory action may be mediated by interactions of GABAergic neurons with each other or with catecholaminergic afferents. We sought to examine the cellular basis for these interactions and their relative frequency. Thus, the ultrastructural morphology of GABAergic neurons and their relation to terminals exhibiting immunoreactivity for the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) were examined in the rat hippocampal formation using combined immunoautoradiographic and peroxidase-antiperoxidase labeling methods. By light microscopy, GABAergic perikarya and processes codistributed most noticeably with TH-containing processes in the hilus of the dentate gyrus (DG) and in strata lucidum, radiatum, and lacunosum-moleculare of the CA3 region of the hippocampus. Thus, these regions were examined further by electron microscopy. In the ultrastructural analysis, GABA-like immunoreactivity (GABA-LI) was detected in neuronal perikarya, dendrites, axons, and axon terminals. The GABA-containing perikarya were large, ovoid (20–40 microns in diameter), and contained abundant cytoplasm and an indented nucleus with one nucleolus. Synaptic junctions on the perikarya and dendrites with GABA-LI were both symmetric and asymmetric. Approximately equal numbers of TH-labeled terminals (19% of 133 in DG; 39% of 26 in CA3) and GABA-containing terminals (19% DG, 15% CA3) formed synapses with GABA-labeled perikarya. The remainder of the presynaptic terminals (62% DG, 46% CA3) were unlabeled, i.e., contained unidentified transmitters. Terminals with GABA-LI (0.5–1.6 microns) contained numerous small clear vesicles and from 0 to 2 large dense-core vesicles. The types of associations formed by terminals with GABA-LI were remarkably similar in the DG and hippocampus proper despite differences in intrinsic cell type and function. Terminals with GABA-LI formed associations with unlabeled perikarya and dendrites (24% of 151 in DG, 25% of 75 in CA3) and synapses with GABA-containing perikarya and dendrites (18% DG, 5% CA3). Additionally, GABAergic terminals converged upon the same perikarya or dendrite as a TH-containing terminal (15% DG, 21% CA3) and were in direct apposition to TH-labeled terminals (19% DG, 20% CA3). The remaining GABAergic terminals (24% DG, 28% CA3) were without any apparent synaptic relations. In both the DG and CA3, the junctions formed by GABAergic terminals were symmetric. Terminals showing colocalization of GABA-LI and TH-I were also detected although rarely.(ABSTRACT TRUNCATED AT 400 WORDS)

Noradrenaline receptors participate in the regulation of GABAergic inhibition in area CA1 of the rat hippocampus.

“…Anatomical data support models I and II, in that a significant portion of GABAergic terminals in the hippocampus form synapses on the same perikarya or dendrites as the noradrenergic terminals (model I), and that there is a close apposition between GABAergic and noradrenergic terminals (model II) (Milner & Bacon, 1989). Electrophysiological data have shown that there is precedence for noradrenaline modulation of both excitatory and inhibitory synaptic transmission.…”

Long‐term potentiation and the mechanisms of memory

“…The effect of picrotoxin is not seen when the p adrenoceptor antagonist, timolol, is co-administered, which suggests that GABAergic synapses in amygdala, septum, and hippocampus are modulated by P-adrenoceptor synapses [Izquierdo et al, 19921, a possibility that is sustained by neuroanatomical findings [Leranth and Frotscher, 1989;Milner and Bacon, 1989;Nieuwenhuys, 19851. Muscimol [Castellano and McGaugh, 19901, bicuculline [Brioni and McGaugh, 19881, and picrotoxin [ McGaugh et al, 19901 are also effective when given systemically. So are most of the benzodiazepines (BZs) (diazepam, chlordiazepoxide, clonazepam), which bind to a specific site of the GABA, receptor arid allosterically enhance the action of GABA or muscimol.…”

“…As commented above, evidence suggests that P-adrenoceptor [ Hopkins and Johnston, 19881 and muscarinic cholinergic receptor [Lin and Phillis, 1991;Markram and Segal, 19921 are involved in the induction of LTP. Abundant neuroanatomical evidence suggests convergence of glutamatergic, GABAergic, cholinergic, and noradrenergic fibers onto hippocampal, amygdala, or septa1 neurons [Leranth and Frotscher, 1989;Milner and Bacon, 1989;Nieuwenhuys, 19851.…”

Noradrenergic Modulation of Electrical Coupling in GABAergic Networks of the Hippocampus

“…Most commonly, varicosities lack postsynaptic specializations and are thought to act functionally by volume transmission (Agnati et al, 1995). However, when synapses are established, GABAergic interneurons are often the preferential postsynaptic targets (Milner and Bacon, 1989). Although both ␣1 noradrenergic receptormediated suppression of a potassium conductance (Bergles et al, 1996) and ␤ noradrenergic receptor-dependent increase of the hyperpolarization-activated current (Maccaferri and McBain, 1996) have been observed in a variety of interneurons, the complete actions of noradrenaline on hippocampal GABAergic networks are not fully understood.…”