Mossy fiber synapses on glutamate decarboxylase-immunoreactive neurons: evidence for feed-forward inhibition in the CA3 region of the hippocampus

Summary Mossy fibers are known to form excitatory synapses on pyramidal neurons in regio inferior of the hippocampus. This study demonstrates that the mossy fibers also establish synaptic contacts with glutamate decarboxylase-immunoreactive, supposedly GABAergic inhibitory neurons in the CA3 region. The observed connection provides a morphological basis for feed-forward inhibition of the pyramidal cells.     

Development of synapses on pyramidal and multipolar non-pyramidal neurons in the visual cortex of rabbits. A combined Golgi-electron microscope study

A combined Golgi-electron microscope method was used to study the ultrastructural maturation of synapses on identified pyramidal and multipolar non-pyramidal neurons in the visual cortex of young and adult rabbits. In samples of 10 (time of eye opening), 14, 20 day old and 7 month old animals, fully impregnated pyramidal neurons within the layers II-V and multipolar non-pyramidal neurons mainly located in lower layer III and layer IV was studied. We found that synapses in 10 and 14 day old animals were occasionally immature in appearance. They were characterized by either a poorly defined postsynaptic band or equal rims of pre- and postsynaptic electron-dense material and could therefore not be classified as Gray type I or II. The distinction between both types of synapses was easier at day 20 and in the adults when the postsynaptic band of the asymmetrical (type I) synapses had become remarkably thicker. In pyramidal neurons the cytoplasmic organelles increased in number during development. Although a few symmetrical synapses were present on dendritic spines of pyramidal neurons in 14 and 20 day old animals, all pyramidal neurons exhibited the same types of synapses on specific sites of their neuronal surface. They received exclusively type II synapses on their somata, type I synapses on their dendritic spines and both types of synapses on their dendritic shafts. However, in the adult animals the frequency of occurrence of type II synapses, especially on basal dendritic shafts, had increased. In some cases only type II and no type I synapses were present. A striking finding in all young and adult animals was that synapses at the borderline between somata and apical dendritic shafts as well as on dendritic spines were frequently complex or interrupted. The characteristic ultrastructural features of adult spine-free and sparsely spiny multipolar non-pyramidal neurons e.g. the many cytoplasmic organelles and type I and II synapses on somata and on dendrites were already present at day 10. After day 10 the number of organelles and synapses increased prominently and in adult animals the different types of synapses on dendrites were located at relatively short intervals of about 4 microns. In contrast with the dendritic shafts of pyramidal neurons many asymmetrical synapses were observed on dendritic shafts of the non-pyramidal neurons analysed in the adult animals. Furthermore, it appeared that the number of synapses on these non-pyramidal neurons is about twice that on pyramidal neurons in day 20 old animals and about four times in adult animals.(ABSTRACT TRUNCATED AT 400 WORDS)     

Agmatine containing axon terminals in rat hippocampus form synapses on pyramidal cells

We examined the cellular and subcellular localization of agmatine in the hippocampal CA1 region by immunocytochemistry. By light microscopy, agmatine-like immunoreactivity (agmatine-LI) was found primarily in the perikarya and dendritic profiles of pyramidal cells and in punctate processes preponderantly in stratum radiatum. Electron microscopy revealed that agmatine-LI was cytoplasmic and concentrated in ‘clusters' associated with mitochondria and tubular vesicles. In stratum radiatum, agmatine-LI was primarily in axons and axon terminals associated with small, synaptic vesicles. The terminals almost exclusively formed asymmetric synapses on the spines of dendrites, many of which originated from pyramidal cells. Some agmatine-LI also was present in shafts and spines of pyramidal cell dendrites and in astrocytic processes. The results demonstrate that agmatine in the hippocampus is found primarily in terminals forming excitatory (asymmetric) synapses on pyramidal cells, some of which contain agmatine-LI. These findings further implicate agmatine as an endogenous neurotransmitter which may be co-stored with -glutamate and may act in part in the rat hippocampus as a blocker of the N-methyl- -aspartate receptor and nitric oxide synthase.     

A combined Golgi-electron microscopic study of non-pyramidal neurons in the CA 1 area of the hippocampus

Summary Non-pyramidal neurons of the CA 1 area of the rat hippocampus were identified with a combined Golgi-electron microscopic method. They were observed to have distinctive light and electron microscopic characteristics that are different from those of pyramidal cells. These features included smooth dendrites, locally arborizing axons, infolded cell nuclei with intranuclear rods or sheets, and a well-developed perikaryal cytoplasm with many organelles. In addition, the axon terminals that contact the somata and dendrites of local circuit neurons may form asymmetric as well as symmetric synapses. The axons of these cells form symmetric synapses with dendrites and somata of pyramidal cells. Some of these features were utilized to identify non-pyramidal neurons of the CA 1 area for studies of connectivity. Degenerating commissural terminals were found to form synapses with the dendrites and somata of non-pyramidal neurons. These results indicate that these neurons are a significant population of hippocampal neurons that may provide feed-forward inhibition of pyramidal neurons.     

Synaptic relationships between a multipolar stellate cell and a pyramidal neuron in the rat visual cortex. A combined Golgi-electron microscope study

Summary Two synapsing and impregnated neurons in the rat visual cortex have been examined by a combined Golgi-electron microscope technique in which the Golgi precipitate is replaced by gold particles. One of the neurons is a stellate cell with smooth dendrites and a well impregnated axon, while the other is a layer III pyramidal neuron. Light microscopy showed some boutons from the axonal plexus of the stellate cell closely apposed to the soma and dendrites of the pyramid and it was predicted that synapses were present at these sites. An electron microscopic examination of serial thin sections, in which the profiles of the impregnated neurons are marked by their content of gold particles, showed most of these predicted synapses to exist. Indeed, axon terminals of the stellate cell formed five symmetric synapses with the cell body of the pyramid, one with the apical dendritic shaft and three with basal dendrites. Reasons are given for believing these synapses to be inhibitory.In addition, it was found that one of the axon terminals of the stellate cell synapsed with one of that cell's own dendrites. The significance of this finding is discussed.     

Bipolar neurons in rat visual cortex: A combined Golgi-electron microscope study

Summary Golgi-impregnated bipolar neurons in rat visual cortex have been examined by both light and electron microscopy. Bipolar neurons are encountered throughout layers II to V and are recognized by their spindle-shaped cell bodies and vertically elongate, narrow dendritic trees which may traverse the cortex from layer II to layer V. Although a single primary dendrite usually extends from each end of the cell body, two primary dendrites may extend from one pole, usually the lower one, and an additional short dendrite may emerge from one side. In the electron microscope gold-toned Golgi-impregnated neurons are seen to have folded nuclear envelopes and except at the poles of the cell body where the dendrites emerge, the nucleus is surrounded by only a thin rim of cytoplasm. Both the cell body and the dendrites form asymmetric and symmetric synapses. Usually the axon of a bipolar neuron arises from one of the primary dendrites and it soon assumes a vertical orientation, to either descend or ascend through the cortical neuropil. Some bipolar neurons have myelinated axons and only the initial portion is impregnated in Golgi preparations, but when they are unmyelinated the axons can be seen to form vertical plexuses and asymmetric synapses. Most commonly the terminals synapse with dendritic spines, some of which are derived from apical dendrites of pyramidal cells, but other terminals synapse with the shafts of apical dendrites, and with the cell bodies and dendrites of nonpyramidal cells.It is apparent that these bipolar neurons are the cells which others have shown to label specifically with antisera to vasoactive intestinal polypeptide (VIP), and it is suggested that the prime role of these cells in the cerebral cortex is to excite the clusters of pyramidal cells.     

Postnatal development of nonpyramidal neurons in the rat hippocampus (areas CA1 and CA3): a combined Golgi/electron microscope study

Summary This study describes the morphological differentiation of nonpyramidal neurons in areas CA1 and CA3 of the rat hippocampus as seen after Golgi-impregnation. Representative neurons were gold-toned and processed for an electron microscopic study of identified cells. We analyzed the postnatal stages P0 (day of birth), P5, P10 and P20. The results can be summarized as follows: 1. On the day of birth nonpyramidal neurons display relatively large cell bodies with short, clumsy dendrites. Great variability of the shape of the cell body and of the orientation of dendrites was observed when compared with the more stereotyped pyramidal neurons. Electron microscopy of identified nonpyramidal neurons revealed small infoldings of the nuclear membrane and immature synapses on the short dendritic shafts of these cells. 2. Developing nonpyramidal neurons from P0 and P5 display growth cones, filopodia, preterminal growth buds, and irregular varicose swellings along the dendrites. 3. Further postnatal development of nonpyramidal neurons is mainly characterized by an increase in dendritic length, paralled by a decrease in growth cones and preterminal growth buds. By means of the electron microscope an increase in the number of mature input synapses on the gold-toned dendritic shafts of identified nonpyramidal neurons was observed. 4. There is a significant developmental difference between nonpyramidal neurons in CA1 and CA3 that was most obvious on P5. Nonpyramidal neurons in CA3 appear more mature, displaying longer dendrites that sometimes traverse through several hippocampal layers. In contrast, the dendrites of nonpyramidal neurons in CA1 are still restricted to the layer of the parent cell body. The earlier differentiation of nonpyramidal neurons in CA3 may result from the earlier formation of neurons in CA3 than in CA1. Longer dendrites of nonpyramidal neurons in CA3, together with an earlier arrival of afferent fibers in this region, suggest that nonpyramidal neurons in CA3 are integrated into inhibitory hippocampal circuits earlier than their counterparts in CA1. 5. On P20, hippocampal nonpyramidal neurons showed all structural characteristics as observed in adult animals both at light and electron microscopic levels. It is concluded that the structural maturation of hippocampal nonpyramidal cells is completed by that postnatal age.In partial fulfilment of the requirements for the degree of Dr. med. at the University of Frankfurt/Main     

Synaptic characteristics of identified pyramidal and multipolar non-pyramidal neurons in the visual cortex of young and adult rabbits. A quantitative Golgi-electron microscope study

The visual cortex of 20 day old rats and rabbits has been considered as mature on the basis of the observations that the dendritic arborization and the overall synaptic population have almost reached their adult stage in these animals. In the present study we have investigated the visual cortex of 20 day and 7 month old (adult) rabbits in order to determine whether this apparent adult appearance also holds for the synaptic organization of individual neurons. Neurons mainly located in layers III and IV of the primary visual cortex (area 17) were Golgi-impregnated, gold toned and deimpregnated and were then, after embedding in plastic, sectioned serially. The number and length of synaptic profiles, and the length of the neuronal boundaries were analysed in every tenth section. From these counts and measurements the size distribution of the synaptic discs, the number of synapses per 100 micron2 neuronal surface and the receptive surface expressed as the percentage of the total neuronal surface covered with synaptic contacts were estimated using stereological methods. At both ages studied, the density of synapses was significantly higher for the non-pyramidal neurons than for the pyramidal neurons. Differences in the amount of receptive surface were parallel to the differences observed for the number of synapses per 100 micron2. At day 20 the receptive surface of the non-pyramidal neurons was significantly larger than that of the pyramidal neurons. The receptive surface of the non-pyramidal neurons in the adult stage was not only larger than that of the pyramidal neurons in the adults, but also larger than that of the day 20 non-pyramidal neurons. From our results the following conclusions can be drawn: (1) The synaptic input received by the pyramidal neurons is mainly established at day 20 of postnatal life, i.e. prior to the establishment of adult visual behaviour. (2) The non-pyramidal neurons complete their maturation in a later stage than the pyramidal neurons. (3) Medium to large sized synaptic contacts are newly formed after day 20 and are mainly added to the synaptic population on dendrites of non-pyramidal neurons. (4) The specific increase in the number of synapses on non-pyramidal neurons is discussed in relation to intracortical inhibition which is thought to be important for the fine regulation of visual function during development.     

Cholecystokinin-immunopositive basket and Schaffer collateral-associated interneurones target different domains of pyramidal cells in the CA1 area of the rat hippocampus.

Two types of GABAergic interneurone are known to express cholecystokinin-related peptides in the isocortex: basket cells, which preferentially innervate the somata and proximal dendrites of pyramidal cells; and double bouquet cells, which innervate distal dendrites and dendritic spines. In the hippocampus, cholecystokinin immunoreactivity has only been reported in basket cells. However, at least eight distinct GABAergic interneurone types terminate in the dendritic domain of CA1 pyramidal cells, some of them with as yet undetermined neurochemical characteristics. In order to establish whether more than one population of cholecystokinin-expressing interneurone exist in the hippocampus, we have performed whole-cell current clamp recordings from interneurones located in the stratum radiatum of the hippocampal CA1 region of developing rats. Recorded neurones were filled with biocytin to reveal their axonal targets, and were tested for the presence of pro-cholecystokinin immunoreactivity.The results show that two populations of cholecystokinin-immunoreactive interneurones exist in the CA1 area (n=15 positive cells). Cholecystokinin-positive basket cells (53%) preferentially innervate stratum pyramidale and adjacent strata oriens and radiatum. A second population of cholecystokinin-positive cells, previously described as Schaffer collateral-associated interneurones [Vida et al. (1998) J. Physiol. 506, 755-773], have axons that ramify almost exclusively in strata radiatum and oriens, overlapping with the Schaffer collateral/commissural pathway originating from CA3 pyramidal cells. Two of seven of the Schaffer collateral-associated cells were also immunopositive for calbindin. Soma position and orientation in stratum radiatum, the number and orientation of dendrites, and the passive and active membrane properties of the two cell populations are only slightly different. In addition, in stratum radiatum and its border with lacunosum of perfusion-fixed hippocampi, 31.6+/-3.8% (adult) or 26.8+/-2.9% (postnatal day 17-20) of cholecystokinin-positive cells were also immunoreactive for calbindin.Therefore, at least two populations of pro-cholecystokinin-immunopositive interneurones, basket and Schaffer collateral-associated cells, exist in the CA1 area of the hippocampus, and are probably homologous to cholecystokinin-immunopositive basket and double bouquet cells in the isocortex. It is not known if the GABAergic terminals of double bouquet cells are co-aligned with specific glutamatergic inputs. However, in the hippocampal CA1 area, it is clear that the terminals of Schaffer collateral-associated cells are co-stratified with the glutamatergic input from the CA3 area, with as yet unknown functional consequences. The division of the postsynaptic neuronal surface by two classes of GABAergic cell expressing cholecystokinin in both the hippocampus and isocortex provides further evidence for the uniform synaptic organisation of the cerebral cortex.     

A combined Golgi-electron microscopic study of the synapses made by the proximal axon and recurrent collaterals of a pyramidal cell in the somatic sensory cortex of the monkey

The synapses made within the cortex by the proximal axon and recurrent collateral branches of a pyramidal cell, the soma of which was at the boundary of layers II and III of the somatic sensory cortex of the monkey, have been studied by the combined Golgi-electron microscopic technique. In a large number of serial sections 62 synapses were found, all of which were asymmetric, 49 being formed by the main axon and 13 by the collaterals. Sixty per cent of the synapses were upon the shafts of dendrites, approximately half of which were identified as being of the large or aspinous stellate cell, and the remainder were upon dendritic spines.If the large stellate cell is inhibitory, then these findings provide a morphological basis for recurrent collateral inhibition.     

Effects of early environment on field CA3a pyramidal neuron morphology in the guinea-pig

There is evidence that early environmental conditions have profound effects on the morphology of the dentate granule cells. The aim of the present study was to obtain information about the effects of early environment on neuron morphology in the hippocampal field CA3, a structure closely linked to the dentate gyrus. The dendritic trees and the somata of field CA3a pyramidal neurons were quantified in Golgi-stained brains of guinea-pigs of both sexes raised in either a social or an isolated environment.Two pyramidal neuron types were found in CA3a, characterized by either a long or a short shaft. Environment affected the apical tree of the long-shaft neurons only in males and that of the short-shaft neurons in both sexes. In isolated males the long-shaft neurons had a decrease in the number of dendritic intersections (62-82%), branching points (76%) and length (71%) in the middle third of the apical tree. The short-shaft neurons had a decrease in the number of intersections at two distal levels only in both isolated males (26, 83%) and females (77, 82%). The shaft spine density was affected by environment in the long-shaft neurons of males only, with a density increase (110%) in isolated males. In both sexes the basal tree of only the long-shaft neurons was affected by environment. Isolated males had a decrease in the number of dendritic intersections (65-88%), primary dendrites (80%) and dendritic length (88%) and isolated females had a decrease in the number of intersections (51-89%), branching points (77%) and dendritic length (85%). The soma major axis of only the long-shaft neurons was affected by environment with a reduction in isolated males (90%) but an increase in isolated females (111%).These results demonstrate dendritic atrophy of CA3a pyramidal neurons following early isolation and a different reactivity to environment of the two CA3a pyramidal neuron types, their apical and basal trees and the two sexes. The dendritic atrophy of CA3a neurons caused by isolation is likely to be associated with an impairment in the physiology of the hippocampal formation and in the forms of memory in which the hippocampal formation plays a major role.     

Peroxide alters neuronal excitability in the CA1 region of guinea-pig hippocampus in vitro

Effects of peroxidative damage on neuronal excitability were investigated with electrophysiological techniques in CA1 pyramidal cells of the hippocampal slice preparation. Hydrogen peroxide alone or combined with ferrous ions (peroxide/iron) is likely to produce hydroxyl free radicals through the Fenton reaction. Intracellularly recorded excitatory postsynaptic potentials and inhibitory postsynaptic potentials were significantly reduced by exposure to peroxide, while responses to iontophoretically applied GABA and glutamate were unaffected. These results suggest that peroxide has presynaptic actions. Peroxide and peroxide/iron also increased frequency adaptation; after exposure, neurons fired fewer action potentials at a lower frequency in response to the same depolarizing current step. A voltage clamp analysis revealed that the potassium currents were unaffected by peroxide/iron. Calcium current was not obviously altered by exposure to peroxide. Sodium spike threshold was also unaffected. Calcium spike threshold was significantly increased by peroxide. This action of peroxide may underlie its presynaptic actions. It is concluded that peroxide produces both presynaptic and postsynaptic damage. This damage is likely to result from the production of free radicals which have been postulated to underlie a number of pathological states.     

Pioneering a golden age of cerebral microcircuits: the births of the combined Golgi-electron microscope methods

Theodor W. Blackstad devised methods by which the synaptic connectivity of neuron somata and their dendritic and axonal processes in the CNS could be analyzed by the combined use of light and electron microscope techniques. His first publication on that subject dates from 1965 and was contemporary to the independent research by William K. Stell. The Golgi method was an obvious neuronal marker at those times, and Blackstad and Stell showed that the Golgi precipitate is electron-dense and intracellular and, therefore, it could help identify in the electron microscope, with great accuracy, profiles of neurons initially visualized in light microscopy. Besides this convergent research, Blackstad demonstrated for the first time that anterograde axonal degeneration could be combined with the Golgi-electron microscope method, allowing the identification of the neurons whose dendritic or somatic profiles were postsynaptic to the severed axonal afferent projections. Last, but not least, Blackstad pioneered de-impregnation techniques for electron microscopy of Golgi preparations. This had a great impact in the study of synaptic circuitry. The present account is a remembrance of the events that linked these early attempts with the development of a de-impregnation method based on gold toning by Alan Peters and the present author.     

BK potassium channels control transmitter release at CA3–CA3 synapses in the rat hippocampus

Augmentation is a component of short-term synaptic plasticity with a gradual onset and duration in seconds. To investigate this component at the corticogeniculate synapse, whole cell patch-clamp recordings were obtained from principal cells in a slice preparation of the rat dorsal lateral geniculate nucleus. Trains with 10 stimuli at 25 Hz evoked excitatory postsynaptic currents (EPSCs) that grew in amplitude, primarily from facilitation. Such trains also induced augmentation that decayed exponentially with a time constant τ= 4.6 ± 2.6 s (mean ± standard deviation). When the trains were repeated at 1–10 s intervals, augmentation markedly increased the size of the first EPSCs, leaving late EPSCs unaffected. The magnitude of augmentation was dependent on the number of pulses, pulse rate and intervals between trains. Augmented EPSCs changed proportionally to basal EPSC amplitudes following alterations in extracellular calcium ion concentration. The results indicate that augmentation is determined by residual calcium remaining in the presynaptic terminal after repetitive spikes, competing with fast facilitation. We propose that augmentation serves to maintain a high synaptic strength in the corticogeniculate positive feedback system during attentive visual exploration.     

Effects of dihydropyridines on calcium currents in CA3 pyramidal cells in slice cultures of rat hippocampus

Slow inward Ca-currents were recorded from CA3 pyrimadal cells in rat hippocampus slice cultures when these cells were voltage-clamped at −40 mV and depolarizing commands applied. Ca-currents were increased in amplitude by the dihydropyridine Ca-agonist BAY K8644 (0.1–1 μM) and reduced by the Ca-antagonists nifedipine and PY 108-068 (0.1–1 μM). Ca-current inhibition by the latter could be temporarily relieved by membrane hyperpolarization. In unclamped cells, dihydropyridines did not alter membrane potential, Ca-spike amplitude, excitatory or inhibitory synaptic current amplitude, or spontaneous synaptic activity. Their principal effects were to alter the threshold for Ca/Ba spike generation and for pitrazepin-induced burst-depolarization. BAY K8644 also induced an after-spike following the normal Na spike, which was reduced by PY 108-068.

It is concluded that the slow inward Ca-current in hippocampal neurones is sensitive to dihydropyridine drugs and that the absence of functional effects of antagonists is due to other causes such as the voltage-dependence of dihydropyridine block and the presence of an additional transient Ca-current which may be less sensitive to block.     

Study of the rat neostriatum using a combined Golgi-electron microscope technique and serial sections

A large number of discrepancies exist among the results of cytological studies of the cell types in the neostriatum of the adult rat. In order to clarify understanding of this problem, a study of these cell types was made using theFaire´n, Peters &Saldanha (1977) combined Golgi-electron microscope method and serial sections.Three kinds of cells were identified in Golgi material, according to cell body size and process morphology i.e. giant, small and medium-sized cells, the latter consisting of four different types.Three gold-toned cells of each cell type were completely cut by serial sections and examined in the electron microscope. Their cytological characteristics, such as nuclear ultrastructure, the aspect, frequency and distribution of cytoplasmic organelles and the dendrite morphology are reported for all cell types encountered in Golgi preparations. Special reference is given to the criteria allowing identification of the four types of medium-sized neurons (types I, II, III and IV). Only one type of giant neuron (type V) was identified. A striking but still unexplained fact is the occurrence of nuclear inclusions (bundles of microfilaments and crystalloids) only in types II, III, IV and V, whereas the type I cells, which correspond to the spiny medium-sized neurons, never display such structures. Direct evidence has been provided that small cells (type VI) lack an axon and synapses on their soma and processes. It is suggested that these cells are not neurons but most likely a type of glial cell.Consequently it is suggested that only five neuron types are present in the neostriatum of the adult rat.     

Localization of tetrodotoxin-sensitive field potentials of CA1 pyramidal cells in the rat hippocampus

1. The role of tetrodotoxin (TTX)-sensitive (Na+) channels in the generation of antidromic and orthodromic field potentials of the CA1 pyramidal cell population was examined by local application of TTX in the in vitro rat hippocampal slice preparation. 2. The sensitivity of alvear (antidromic) and stratum oriens (SO)-evoked potentials to TTX application (10-100 microM) was tested in stratum pyramidale and over the entire extent of pyramidal cell apical dendrites in stratum radiatum. Stratum radiatum (SR)-evoked potentials were examined at the level of pyramidal cell bodies and over the proximal 200 microns of the apical dendritic region. 3. Pressure application of TTX confined to stratum pyramidale or regions of stratum radiatum selectively blocked the negative component of antidromic and SO-evoked population discharge in the cell body layer and over the initial 200 microns of stratum radiatum. 4. SR stimulation evoked a complex field potential in the proximal stratum radiatum (less than 150 microns) composed of at least three components: 1) A short-duration (approximately 3 ms) negativity of shorter peak latency than the population spike recorded simultaneously in stratum pyramidale. This potential was highly sensitive to TTX and appeared to be instrumental in the generation of the cell body population response. 2) A long-duration negativity (approximately 20 ms) evoked at stimulation strengths that were subthreshold for both the short-duration negativity in proximal stratum radiatum and the cell body population spike. Although apparently less sensitive to TTX, this potential was reduced in amplitude with repeated TTX application; and 3) a slow (approximately 12 ms) positive-going potential that was only observed after eliminating all TTX-sensitive conductance mechanisms in the proximal stratum radiatum. 5. The latency difference between the SR-evoked short-duration negativity of proximal stratum radiatum and the population spike in stratum pyramidale decreased or reversed during the course of multiple discharge induced by the addition of bicuculline or picrotoxin (5-10 microM) to the perfusate. 6. These data indicate the presence of TTX-sensitive presumed Na+ channels over the initial 200 microns of pyramidal cell apical dendrites capable of supporting active conduction of population discharge evoked by antidromic or SO stimulation. The sensitivity of SR-evoked potentials to TTX suggests that a synaptic potential generated in the distal apical dendrites is capable of triggering both a slow active depolarization and a fast spike-like discharge in the proximal apical dendritic region.(ABSTRACT TRUNCATED AT 400 WORDS)     

Subicular lesions cause dendritic atrophy in CA1 and CA3 pyramidal neurons of the rat hippocampus

The subiculum is a major source of output projections from hippocampus to cortical and subcortical regions. Our previous studies have demonstrated the selective loss of CA1 pyramidal neurons of the hippocampus, and operant and spatial learning impairment in subicular lesioned rats [Govindaiah et al. (1997) Brain Res. 745, 121-126; Laxmi et al. (1999) Brain Res. 816, 245-148]. In the present study, the effect of ibotenate lesions of the subiculum on the dendritic morphology of CA1 and CA3 pyramidal neurons of the hippocampus was investigated in 30-day-old male Wistar rats. The ventral subiculum was lesioned bilaterally with multiple injections of ibotenic acid, stereotaxically. The dendritic branching points and intersections were studied in apical and basal dendrites up to 320 and 160 microm, respectively, in Golgi-impregnated CA1 and CA3 pyramidal neurons of the hippocampus. The results revealed a significant (P<0.001) decrease in the number of dendritic branching points, intersections and total number of dendrites in both apical and basal dendrites of CA1, as well as CA3 pyramidal neurons of the hippocampus. It is surprising that the subicular lesions caused dendritic atrophy of CA3 neurons without affecting the cell density.The results of the present study demonstrate the dendritic atrophy of hippocampal neurons following selective subicular lesions. This might be responsible for the impairments in operant and spatial learning tasks in these rats as observed in our earlier studies. In addition, hippocampal damage is also associated with an impairment in the process of the active monitoring of movements in space, rather than place learning per se [Whishaw (1998) Neurosci. biobeh. Rev. 22, 209-220]. Accordingly, further studies are required to correlate the differential effect of subicular lesions on impairments in learning and movement in space in rats.