Michael Frotscher

A GABAergic axo-axonic cell in the fascia dentata controls the main excitatory hippocampal pathway.

Neuronal discharge is very efficiently blocked by inhibitory synapses on the axon initial segment. Here we describe a novel type of gamma-aminobutyric acid (GABA)-ergic inhibitory neurons in the rat fascia dentata that exclusively forms synaptic contacts with the axon initial segments of numerous dentate granule cells. This way the main excitatory pathway of the hippocampal formation which interconnects the fascia dentata with the hippocampus proper is controlled. We hypothesize that hypofunction of this inhibitory neuron causes overexcitation in the main excitatory pathway which could play a role in epilepsy.

Commissural afferents innervate glutamate decarboxylase immunoreactive non-pyramidal neurons in the guinea pig hippocampus.

Abstract The innervation of GABAergic hippocampal neurons by commissual fibers was investigated in the guinea pig by a combined anterograde degeneration - immunocytochemical technique. Presumed GABAergic neurons were identified by immunocytochemistry for glutamate decarboxylase (GAD) and the commissural fibers by electron-dense degeneration following contralateral transection of the fimbria. Commissural afferents were found to establish asymmetric synaptic contacts with non-pyramidal GAD-immunoreactive neurons located in subpyramidal and suprapyramidal zones of region CA1. The observed connection suggests that inhibition of pyramidal cells may occur in a feed-forward manner as postulated by electrophysiological studies.

Entorhinal fibers form synaptic contacts on parvalbumin-immunoreactive neurons in the rat fascia dentata

The entorhinal cortex gives rise to a dense projection to the outer two-thirds of the dentate molecular layer. The main target neurons are the granule cells. This study demonstrates that entorhinal fibers labeled by anterograde degeneration also terminate on parvalbumin-containing non-granule cells in the rat fascia dentata. Since the calcium-binding protein parvalbumin was recently found coexistent with gamma-aminobutyric acid in inhibitory hippocampal neurons, the described connection provides evidence for a role of entorhinal fibers in feed-forward inhibition of the granule cells.

Mossy fibres form synapses with identified pyramidal basket cells in the CA3 region of the guinea-pig hippocampus: a combined Golgi-electron microscope study

SummaryMossy fibres, i.e. the axons of dentate granule cells, terminate with characteristic giant boutons on large spines or excrescences of the pyramidal cells in regio inferior of the hippocampus. In addition to pyramidal cells there are several types of non-pyramidal neuron which extend their dendrites into the termination zone of mossy fibres. By using the combined Golgi-electron microscope technique mossy fibre terminals were found, which established asymmetric synaptic contacts with both spines of pyramidal cells and smooth dendrites of identified (Golgi-stained) pyramidal basket cells in the CA3 region of the guinea-pig hippocampus. The observed synaptic connection with pyramidal basket cells suggests an involvement of the mossy fibre system in feed-forward inhibition of the hippocampal pyramidal neurons.

Cholinergic neurons in the hippocampus

SummaryWe report here on cholinergic neurons in the rat hippocampal formation that were identified by immunocytochemistry employing a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme. In general, ChAT-immunoreactive cells were rare, but were observed in all layers of the hippocampus proper and fascia dentata with a preponderance in zones adjacent to the hippocampal fissure and in the part of CA1 bordering the subiculum. All immunoreactive cells found were non-pyramidal neurons. They were relatively small with round or ovoid perikarya, which gave rise to thin spine-free dendrites. These hippocampal neurons were very similar to ChAT-immunoreactive cells in the neocortex of the same animals but were quite different from cholinergic neurons in the basal forebrain, medial septal nucleus, and neostriatum, which were larger and more intensely immunostained.Electron-microscopic analysis of ChAT-immunoreactive cells in the hippocampus and fascia dentata revealed synaptic contacts, mainly of the asymmetric type, on cell bodies and smooth proximal dendrites. The nuclei of the immunoreactive cells exhibited deep indentations, which are characteristic for non-pyramidal neurons.Our results provide evidence for an intrinsic source of the hippocampal cholinergic innervation in addition to the well-established septo-hippocampal cholinergic projection.

Fine structure and synaptic connections of identified neurons in the rat fascia dentata

SummaryA survey is given of the synaptic connections of identified neurons in the rat fascia dentata based on our own Golgi/electron microscopic and light and electron microscopic immunocytochemical findings as well as on results obtained from the literature. The report largely deals with the dominating cell type in the region, the dentate granule cell. Of the various types of hilar cells, the GA-BAergic neurons, particularly the inhibitory basket cells, are taken into account. Differences in fine structure between granule cells and basket cells as well as mutual synaptic connections between these two types of dentate neurons are elaborated. This survey may provide a basis for further neurophysiological and pharmacological studies on these cells.

Neurogenesis of GABAergic neurons in the rat dentate gyrus: A combined autoradiographic and immunocytochemical study

Neurogenesis of GABAergic neurons in the rat area dentata was studied combining [3H]thymidine autoradiography with immunostaining for glutamate decarboxylase (GAD), the gamma-aminobutyric acid (GABA) synthesizing enzyme. GAD immunocytochemistry stained many neurons located mainly in the hilar region but also in the granular and molecular layers. Granule cells were not immunoreactive. On embryonic day (E) 14, [3H]thymidine injection labelled 12.8% of GAD-positive (+) neurons in sections of the area dentata processed at an age of 40 days postnatally. This proportion decreased to 1.8% on E17 and to 1% on E18. No GAD (+) neurons were labelled by thymidine injection on E19, while non-immunoreactive granule cells and CA4 pyramids were still labelled, indicating persisting neurogenesis of those cells.

Central cholinergic synaptic transmission

Cholinergic neurons, pathways and synapses.- Behavioral neuroanatomy of cholinergic innervation in the primate cerebral cortex.- Afferent connections of the forebrain cholinergic projection neurons, with special reference to monoaminergic and peptidergic fibers.- Central cholinergic synapses: The septohippocampal system as a model.- Cholinergic-GABAergic synaptic interconnections in the rat amygdaloid complex: An electron microscopic double immunostaining study.- Topography of ?NGF receptor-positive and AChE-reactive neurons in the central nervous system.- Chol-1: A cholinergic-specific ganglioside of possible significance in central nervous system neurochemistry and neuropathology.- Acetylcholine-induced postsynaptic potentials and excitatory changes.- Pharmacological characterization of muscarinic responses in rat hippocampal pyramidal cells.- Mediation of acetylcholines excitatory actions in central neurons.- Presynaptic cholinergic action in the hippocampus.- Opposing effects of acetylcholine on the two classes of voltage-dependent calcium channels in hippocampal neurons.- Muscarinic slow EPSPs in neostriatal and hippocampal neurons in vitro.- Carbachol and pirenzepine discriminate effects mediated by two muscarinic receptor subtypes on hippocampal neurons in vitro.- Cholinergic activation of medial pontine reticular formation neurons in vitro.- Cholinergic responses in human neocortical neurones.- Cholinergic modulation of hippocampal epileptic activity in vitro.- The cholinergic nucleus basalis: A key structure in neocortical arousal.- Cholinergic mechanisms in the telencephalon of cat and chicken.- Cholinergic receptor types and their modulation.- Central nicotinic acetylcholine receptors in the chicken and Drosophila CNS: Biochemical and molecular biology approaches.- Modulation of the sensitivity of nicotinic receptors in autonomic ganglia.- Muscarinic modulation of acetylcholine release: Receptor subtypes and possible mechanisms.- Characterization of muscarinic receptors modulating acetylcholine release in the rat neostriatum.- Distribution of cholinergic receptors in the rat and human neocortex.- Acetylcholine and plasticity of the CNS.- Effects of chronic in vivo replacement of choline with a false cholinergic precursor.- Development of the septohippocampal projection in vitro.- A role of basic fibroblast growth factor for rat septal neurons.- Survival, growth and function of damaged cholinergic neurons.- Restoration of cholinergic circuitry in the hippocampus by foetal grafts.- Effects of colchicine treatment on the cholinergic septohippocampal system.- Effect of early visual pattern deprivation on development and laminar distribution of cholinergic markers in rat visual cortex.- The role of muscarinic acetylcholine receptors in ocular dominance plasticity.- Acetylcholine-dopamine balance in striatum: Is it still a target for antiparkinsonian therapy?.

Glutamate decarboxylase-immunoreactive neurons in the aging rat hippocampus are more resistant to ischemia than CA1 pyramidal cells

Glutamate decarboxylase (GAD)-immunoreactive, supposedly GABAergic inhibitory, neurons in various fields of the rat hippocampus and pyramidal cells in area CA1 were quantified 1 week after transient cerebral ischemia by 4-vessel occlusion. Whereas the number of CA1 pyramidal cells in Toluidine blue-stained semithin sections were found reduced by 50% when compared with controls there was no loss of GAD-immunoreactive cells in vibratome sections of hippocampus proper and fascia dentata. These data suggest that GABAergic hippocampal neurons are more resistant to ischemia than CA1 pyramidal cells.

Differentiation of granule cells in relation to GABAergic neurons in the rat fascia dentata: combined Golgi/EM and immunocytochemical studies

SummaryGolgi impregnation was used to study the dendritic differentiation of granule cells in the rat fascia dentata. The impregnated granule cells were gold-toned allowing for a fine structural study of the same identified neurons and of the input synapses onto their cell bodies and dendrites. Due to the long postnatal formation of these cells it was possible to describe a sequence of maturational stages coexisting on the same postnatal day (P5). Characteristic features of the dendritic development of granule cells were i) occurrence of varicose swellings along the dendrites, ii) growth cones on dendritic tips, iii) transient formation of basal dendrites, and iv) progressive development of dendritic spines. Incoming synapses on the differentiating granule cells were mainly found on dendritic shafts. Their membrane specializations were symmetric. At least some of these symmetric synapses were GABAergic because immunostaining of Vibratome sections from the same postnatal stage (P5) demonstrated a well-developed GABAergic axon plexus in the fascia dentata (antibodies against glutamate decarboxylase (GAD), the GABA synthesizing enzyme). Electron microscopy of the immunostained axon plexus revealed numerous GABAergic terminals that formed symmetric synaptic contacts, mainly on shafts of differentiating dendrites but also on cell bodies of granule cells. Our results thus indicate that the plexus of inhibitory GABAergic axons is already well developed at a stage when the target neurons, the granule cells, are still being formed.