Interneurons of the hippocampus

"Embryogenesis is in some way a model system. It has always been distinguished by the exactitude even punctitio, of its anatomical descriptions. An experiment by one of the great masters of embryology could be made the text of a discourse on scientific method. But something is wrong, or has been wrong. There is no theory of development in the sense in which Mendelism is a theory that accounts for the results of breeding experiments. There has therefore been little sense of progression or timeliness about embryological research. Of many papers delivered at embryological meetings, however good they may be in themselves . . . one too often feels that they might have been delivered five years beforehand without making anyone much the wiser, or deferred for five years without making anyone conscious of a great loss" (1). This feeling of frustration so incisively conveyed by these considerations by P. Medawar, pervaded, in the forties, the field of experimental embryology which had been enthusiastically acclaimed in the mid-thirties, when the upper lip of the amphibian blastopore brought this area of research to the forefront of the biological stage. The side branch of experimental neuroembryology, which had stemmed out from the common tree and was entirely devoted to the study of the tropic interrelations between neuronal cell populations and between these and the innervated organs and tissues, was then in its initial vigorous growth phase. It in turn suffered from a sharp decrease in the enthusiasm that had inflamed the pioneers in this field, ever since R. G. Harrison delivered his celebrated lecture on this topic at the Royal Society in London in 1935 (2). Although the alternate "wax and wane" cycles are the rule rather than the exception in all fields of human endeavor, in that of biological sciences the "wane" is all too often indicative of a justified loss of faith in the rational and methodical approach that had at first raised so much hope. A brief account of the state-of-the-art of experimental neuroembryology in the

https://science.sciencemag.org/content/sci/237/4819/1154.full.pdf

The nerve growth factor 35 years later

The neurotrophins are a family of proteins that are essential for the development of the vertebrate nervous system. Each neurotrophin can signal through two different types of cell surface receptor — the Trk receptor tyrosine kinases and the p75 neurotrophin receptor. Given the wide range of activities that are now associated with neurotrophins, it is probable that additional regulatory events and signalling systems are involved. Here, I review recent findings that neurotrophins, in addition to promoting survival and differentiation, exert various effects through surprising interactions with other receptors and ion channels.

/pdf/neurotrophins-and-their-receptors-a-convergence-point-for-3hfqpg5jyn.pdf

Neurotrophins and their receptors: a convergence point for many signalling pathways.

The neurotrophins are a small group of dimeric proteins that profoundly affect the development of the nervous system of vertebrates. Recent studies have established clear correlations between the survival requirements for different neurotrophins of functionally distinct subsets of sensory neurons. The biological role of the neurotrophins is not limited to the prevention of programmed cell death of specific groups of neurons during development. Neurotrophin-3 in particular seems to act on neurons well before the period of target innervation and of normally occuning cell death. In animals lacking functional neurotrophin or receptor genes, neuronal numbers do not seem to be massively reduced in the CNS, unlike in the PNS. Finally, rapid actions of neurotrophins on synaptic efficacy, as well as the regulation of their mRNAs by electrical activity, suggest that neurotrophins might play important roles in regulating neuronal connectivity in the developing and in the adult central nervous system.

Physiology of the neurotrophins

Trophic factors and neuronal survival

Neurons in the rat medial septum (MS) and vertical limb of the diagonal band of Broca (VDB) undergo a rapid and severe cell death after transection of their dorsal projection to the hippocampus by aspiration of the ipsilateral fimbria fornix and supracallosal striae. By 2 weeks posttransection, the extent of neuronal loss was 50% of the total neurons and 70% of the cholinergic neurons in the MS and 30% of the total neurons and 40% of the cholinergic neurons in the VDB. We hypothesized that (i) the death was due to the loss of a hippocampus-derived neuronotrophic factor, and (ii) exogenous nerve growth factor (NGF) might provide trophic support to the MS/VDB cholinergic neurons, in light of recent reports that the septal diagonal band cholinergic neurons are responsive to NGF and that NGF is present and produced in the hippocampus. In the present study, we attempted to prevent the transection-induced neuronal death by continuous infusion of exogenous 7S NGF (1 microgram/wk) through an intraventricular cannula device. We report here that NGF treatment significantly reduces both the total neuronal and cholinergic neuronal death found 2 weeks after fimbria fornix transection; there was a sparing of 50% of the neurons in the MS and essentially 100% of those in the VDB that otherwise would have died. We conclude that NGF also has a protective effect on noncholinergic neurons since calculations indicate that 80% of the NGF-affected neurons are noncholinergic.

https://www.pnas.org/content/pnas/83/23/9231.full.pdf

Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection

Intragranular and supragranular mossy fibers arise from granule cells and are present in the dentate gyrus of hippocampi from kindled and epileptic animals. The intragranular fibers often appear as fibers perpendicular to the long axis of the granule cell layer at periodic intervals. Rats and gerbils were analyzed to determine whether such mossy fibers are also associated with nongranule cells (including the basket cells), which send their apical dendrites through this layer with a periodicity similar to that of mossy fibers. The results for rats and both epileptic and nonepileptic gerbils show that many intragranular mossy fibers are apposed to the surfaces of the somata and apical dendrites of basket cells where they form asymmetric synapses. This plexus of mossy fiber axons appears to follow the dendrites of these neurons into the inner molecular layer. Based on previous data indicating that basket cells are GABAergic inhibitory neurons, the present findings in normal rats and both types of gerbils suggest that intragranular and supragranular mossy fibers provide additional circuitry for feedback inhibition to granule cells. It is possible that under pathological conditions, such as denervation or kindling, these fibers sprout and form synapses with granule cells.

Gary M. Peterson

Papers

Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection

Intragranular mossy fibers in rats and gerbils from synapses with the somata and proximal dendrites of basket cells in the dentate gyrus

Loss of GABAergic neurons in medial septum after fimbria-fornix transection.

Fate of septohippocampal neurons following fimbria-fornix transection: a time course analysis.

Anterograde and retrograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L) from the globus pallidus to the striatum of the rat