The hippocampus, in particular the neocortex-hippocampus-neocortex circuit, is widely believed to be crucial in memory. Information flow in this circuit is strongly influenced by relatively sparse afferents derived from subcortical centres, such as the septum, involved in arousal, emotions and autonomic control. A powerful mechanism, by which numerically small inputs can produce profound effects, is feed-forward inhibition, that is, the activation of local inhibitory interneurons, which, in turn, control the activity of large populations of principal cells in the hippocampus. An example is the cholinergic input to the hippocampus from the septum, which is likely to be involved in feed-forward operations. Here, we demonstrate the existence of a circuit underlying another powerful mechanism of subcortical control of hippocampal information processing. We show that GABA-containing afferents originating in the septum innervate most of the GABA-containing interneurons in the hippocampus, making many synaptic contacts with each of them. Activation of the GABA-containing neurons in the septum is likely to lead to disinhibition of the principal neurons in the hippocampal formation and so this pathway is probably crucial in the induction of hippocampal electrical activity patterns, and may be involved in NMDA (N-methyl-D-aspartate) receptor-mediated functions, such as memory, in a permissive manner.
Presynaptic inhibition of primary muscle spindle (group Ia) afferent terminals in motor nuclei of the spinal cord plays an important role in regulating motor output and is produced by a population of GABAergic axon terminals known as P boutons. Despite extensive investigation, the cells that mediate this control have not yet been identified. In this work, we use immunocytochemistry with confocal microscopy and EM to demonstrate that P boutons can be distinguished from other GABAergic terminals in the ventral horn of rat and mouse spinal cord by their high level of the glutamic acid decarboxylase (GAD) 65 isoform of GAD. By carrying out retrograde labeling from lamina IX in mice that express green fluorescent protein under the control of the GAD65 promoter, we provide evidence that the cells of origin of the P boutons are located in the medial part of laminae V and VI. Our results suggest that P boutons represent the major output of these cells within the ventral horn and are consistent with the view that presynaptic inhibition of proprioceptive afferents is mediated by specific populations of interneurons. They also provide a means of identifying P boutons that will be important in studies of the organization of presynaptic control of Ia afferents.GABA ͉ Ia afferent ͉ presynaptic inhibition T he inhibitory transmitter GABA is used by many neurons in the spinal cord and generates both postsynaptic inhibition at axo-dendritic and axo-somatic synapses and presynaptic inhibition at axo-axonic synapses (1). GABA is synthesized by the enzyme glutamic acid decarboxylase (GAD), and Abs against GAD have been used to identify GABAergic axonal boutons in the spinal cord (2, 3). More recently, two forms of the enzyme have been identified, and based on their molecular weights these forms have been named GAD65 and GAD67 (4). Both forms are present in the ventral horn of the rat spinal cord but have a very different distribution (5, 6). The majority of GABAergic boutons throughout the ventral horn show strong GAD67 immunoreactivity and a low level of GAD65. However, there are clusters of boutons in lamina IX that contain very high levels of GAD65. We have suggested (6) that these clusters may correspond to the P boutons that form axo-axonic synapses with terminals of group Ia afferents (7-10). In this work, we have used a variety of approaches to confirm this hypothesis and to identify the cells of origin of these boutons. MethodsAll experiments were approved by the Ethical Review Process Applications Panel of the University of Glasgow or the Animal Care and Protection Committee at the University of Debrecen and were performed in accordance with the U.K. Animals (Scientific Procedures) Act 1986 and the European Communities Council Directives. Immunocytochemical reactions were performed on free-floating 60-m transverse Vibratome sections that had been treated with 50% ethanol for 30 min to enhance Ab penetration. Abs were diluted in PBS with 0.3% Triton X-100 (except on sections used for EM).Primary Afferent Labeling. Transgang...
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