Charles E. Ribak

Bio: Charles E. Ribak is an academic researcher from University of California, Irvine. The author has contributed to research in topics: Dentate gyrus & Hippocampal formation. The author has an hindex of 60, co-authored 153 publications receiving 12295 citations. Previous affiliations of Charles E. Ribak include Boston University & City of Hope National Medical Center.

Neurons born in the adult dentate gyrus form functional synapses with target cells

Abstract: Adult neurogenesis occurs in the hippocampus and the olfactory bulb of the mammalian CNS. Recent studies have demonstrated that newborn granule cells of the adult hippocampus are postsynaptic targets of excitatory and inhibitory neurons, but evidence of synapse formation by the axons of these cells is still lacking. By combining retroviral expression of green fluorescent protein in adult-born neurons of the mouse dentate gyrus with immuno-electron microscopy, we found output synapses that were formed by labeled terminals on appropriate target cells in the CA3 area and the hilus. Furthermore, retroviral expression of channelrhodopsin-2 allowed us to light-stimulate newborn granule cells and identify postsynaptic target neurons by whole-cell recordings in acute slices. Our structural and functional evidence indicates that axons of adult-born granule cells establish synapses with hilar interneurons, mossy cells and CA3 pyramidal cells and release glutamate as their main neurotransmitter.

Aspinous and sparsely-spinous stellate neurons in the visual cortex of rats contain glutamic acid decarboxylase.

Abstract: Glutamic acid decarboxylase (GAD), the enzyme that synthesizes the neurotransmitter gamma-amino-butyric acid (GABA), has been localized in the rat visual cortex by immunocytochemical methods with both light and electron microscopy. In both colchicine-injected and non-injected preparations of the visual cortex, GAD-positive reaction product was observed in somata, proximal dendrites and axon terminals of non-pyramidal neurons. The GAD-positive terminals were observed to form symmetric synaptic junctions most commonly with dendritic shafts and somata of pyramidal and stellate neurons and less frequently with initial axon segments of pyramidal neurons and dendritic spines. In colchicine-injected preparations, GAD-positive somata were located in all cortical layers including the immediately subjacent white matter. In contrast, sections from non-injected rats displayed GAD-positive somata within a superficial and a deep cortical band. The GAD-positive somata observed in both types of preparations received both symmetric and asymmetric synaptic junctions, lacked apical dendrites, and had radially oriented dendrites of small diameter. These characteristics of GAD-positive neurons indicate that they are aspinous and sparsely-spinous stellate neurons. The localization of GAD within these neurons in combination with physiological and pharmacological data indicate that these local circuit neurons mediate GABA-ergic inhibition in the neocortex.

The GABA neurons and their axon terminals in rat corpus striatum as demonstrated by GAD immunocytochemistry.

Abstract: Glutamic acid decarboxylase (GAD, EC 4.1.1.15), the enzyme which catalyzes the α-decarboxylation of L-glutamate to form the neurotransmitter γ-aminobutyric acid (GABA), was localized immunocytochemically in neurons of rat neostriatum, pallidum and entopeduncular nucleus. A large amount of GAD-positive reaction product was observed in both the pallidum and entopeduncular nucleus in light microscopic preparations and was localized ultrastructurally to axon terminals that surrounded dendrites and large somata. In the neostriatum the relative numbers of GAD-positive axon terminals per unit area were substantially less than in the pallidum. GAD-positive terminals predominantly formed symmetric synapses with somata, dendrites and spines, but a small number of them formed asymmetric synapses with either dendrites or spines. The presence of GAD within these terminals is consistent with results of other investigations which have indicated that the striatopallidal and striatoentopeduncular pathways as well as neostriatal local circuit neurons and/or collaterals from neostriatal projection neurons, use GABA as a neurotransmitter. GAD-positive reaction product was also localized within the somata and dendrites of neostriatal and pallidal neurons in colchicine-injected preparations. The GAD-positive somata in the pallidum were medium-sized neurons and since such cells project to the substantia nigra, our results are in agreement with those from other studies which demonstrate a GABAergic, pallidonigral pathway. In the neostriatum, GAD-positive somata were identified light microscopically as medium-sized neurons with either round or fusiform shapes. Electron microscopic examinations also showed GAD-positive reaction product within the perikaryal and dendritic cytoplasm of these neurons, as well as in dendritic spines. These findings are in accord with the results of studies which have indicated that medium-sized, spinous neurons of the neostriatum give rise to a GABAergic, striatonigral pathway. The significance of GAD localization within these neostriatal neurons is discussed in relation to recent findings which show that substance P is contained within this same class of striatonigral projection neuron.

The synaptic organization of the brain

Abstract: Introduction to synaptic circuits, Gordon M.Shepherd and Christof Koch membrane properties and neurotransmitter actions, David A.McCormick peripheral ganglia, Paul R.Adams and Christof Koch spinal cord - ventral horn, Robert E.Burke olfactory bulb, Gordon M.Shepherd, and Charles A.Greer retina, Peter Sterling cerebellum, Rodolfo R.Llinas and Kerry D.Walton thalamus, S.Murray Sherman and Christof Koch basal ganglia, Charles J.Wilson olfactory cortex, Lewis B.Haberly hippocampus, Thomas H.Brown and Anthony M.Zador neocortex, Rodney J.Douglas and Kevan A.C.Martin Gordon M.Shepherd. Appendix: Dendretic electrotonus and synaptic integration.

Alzheimer's disease: a disorder of cortical cholinergic innervation

Abstract: Great emphasis is being placed on identification of neurotransmitter systems involved in the symptomatic manifestations of neurological and psychiatric disorders. In the case of Alzheimer's disease, which now seems to be one of the most common causes of mental deterioration in the elderly, compelling evidence has been developed that acetylcholine-releasing neurons, whose cell bodies lie in the basal forebrain, selectively degenerate. These cholinergic neurons provide widespread innervation of the cerebral cortex and related structures and appear to play an important role in cognitive functions, especially memory. These advances reflect a close interaction between experimental and clinical neuroscientists in which information derived from basic neurobiology is rapidly utilized to analyze disorders of the human brain.

Ferrier Lecture: Functional Architecture of Macaque Monkey Visual Cortex

Abstract: Of the many possible functions of the macaque monkey primary visual cortex (striate cortex, area 17) two are now fairly well understood. First, the incoming information from the lateral geniculate bodies is rearranged so that most cells in the striate cortex respond to specifically oriented line segments, and, second, information originating from the two eyes converges upon single cells. The rearrangement and convergence do not take place immediately, however: in layer IVc, where the bulk of the afferents terminate, virtually all cells have fields with circular symmetry and are strictly monocular, driven from the left eye or from the right, but not both; at subsequent stages, in layers above and below IVc, most cells show orientation specificity, and about half are binocular. In a binocular cell the receptive fields in the two eyes are on corresponding regions in the two retinas and are identical in structure, but one eye is usually more effective than the other in influencing the cell; all shades of ocular dominance are seen. These two functions are strongly reflected in the architecture of the cortex, in that cells with common physiological properties are grouped together in vertically organized systems of columns. In an ocular dominance column all cells respond preferentially to the same eye. By four independent anatomical methods it has been shown that these columns have the from of vertically disposed alternating left-eye and right-eye slabs, which in horizontal section form alternating stripes about 400 $\mu $m thick, with occasional bifurcations and blind endings. Cells of like orientation specificity are known from physiological recordings to be similarly grouped in much narrower vertical sheeet-like aggregations, stacked in orderly sequences so that on traversing the cortex tangentially one normally encounters a succession of small shifts in orientation, clockwise or counterclockwise; a 1 mm traverse is usually accompanied by one or several full rotations through 180 degrees, broken at times by reversals in direction of rotation and occasionally by large abrupt shifts. A full complement of columns, of either type, left-plus-right eye or a complete 180 degrees sequence, is termed a hypercolumn. Columns (and hence hypercolumns) have roughly the same width throughout the binocular part of the cortex. The two independent systems of hypercolumns are engrafted upon the well known topographic representation of the visual field. The receptive fields mapped in a vertical penetration through cortex show a scatter in position roughly equal to the average size of the fields themselves, and the area thus covered, the aggregate receptive field, increases with distance from the fovea. A parallel increase is seen in reciprocal magnification (the number of degrees of visual field corresponding to 1 mm of cortex). Over most or all of the striate cortex a movement of 1-2 mm, traversing several hypercolumns, is accompanied by a movement through the visual field about equal in size to the local aggregate receptive field. Thus any 1-2 mm block of cortex contains roughly the machinery needed to subserve an aggregate receptive field. In the cortex the fall-off in detail with which the visual field is analysed, as one moves out from the foveal area, is accompanied not by a reduction in thickness of layers, as is found in the retina, but by a reduction in the area of cortex (and hence the number of columnar units) devoted to a given amount of visual field: unlike the retina, the striate cortex is virtually uniform morphologically but varies in magnification. In most respects the above description fits the newborn monkey just as well as the adult, suggesting that area 17 is largely genetically programmed. The ocular dominance columns, however, are not fully developed at birth, since the geniculate terminals belonging to one eye occupy layer IVc throughout its length, segregating out into separate columns only after about the first 6 weeks, whether or not the animal has visual experience. If one eye is sutured closed during this early period the columns belonging to that eye become shrunken and their companions correspondingly expanded. This would seem to be at least in part the result of interference with normal maturation, though sprouting and retraction of axon terminals are not excluded.