Nitric oxide-containing pyramidal neurons of the subiculum innervate the CA1 area

Neurons and axon terminals containing neuron-specific nitric oxide synthase (nNOS) were examined in the rat subiculum and CA1 area of Ammon's horn. In the subiculum, a large subpopulation of the pyramidal neurons and non-pyramidal cells are immunoreactive for nNOS, whereas in the neighbouring CA1 area of Ammon's horn only non-pyramidal neurons are labelled with the antibody against nNOS. In the pyramidal layer of the subiculum, nNOS-positive axon terminals form both asymmetric and symmetric synapses. In the adjacent CA1 area the nNOS-positive terminals that form symmetric synapses are found in all layers, whereas those terminals that form asymmetric synapses are only in strata radiatum and oriens, but not in stratum lacunosum-moleculare. In both the subiculum and CA1 area, labelled terminals make symmetric synapses only on dendritic shafts, whereas asymmetric synapses are exclusively on dendritic spines. Previous observations demonstrated that all nNOS-positive non-pyramidal cells are GABAergic local circuit neurons, which form exclusively symmetric synapses. We suggest that nNOS-immunoreactive pyramidal cells of the subiculum may innervate neighbouring subicular pyramidal cells and, to a smaller extent, pyramidal cells of the adjacent CA1 area, forming a backward projection between the subicular and hippocampal principal neurons. Electronic Publication     

Hypobaric hypoxia-induced dendritic atrophy of hippocampal neurons is associated with cognitive impairment in adult rats

Simulated hypobaric hypoxia (HBH), resembling high altitude hypoxia severely affects the CNS and results in several physiological changes. The hippocampus is closely associated with learning and memory and an insult to this region affects cognition. Previous studies suggest that rapid or prolonged exposures to HBH are associated with psychomotor and cognitive impairments. The defense personnel, mountain climbers and rescue teams are exposed to such harsh environment and thus it demands a systematic study emphasizing the subtle effects of such extreme environments on cognitive function. Accordingly, this study evaluated the effect of hypobaric hypoxia on structural changes in the principal neurons of the hippocampus and learning in eight-arm radial maze. Adult male Wistar rats, subjected to simulated hypobaric hypoxia equivalent to an altitude of 6000 m for a period of 2 or 7 days, in a hypoxic chamber served as hypoxic group (HY). Rats housed in a similar chamber for the same period of time, without hypoxic exposure served as sham control (SC), while normal control (NC) group of rats were housed in standard laboratory conditions. The dendritic morphology of neurons in cornu ammonis region 1 (CA1) and cornu ammonis region 3 (CA3) was studied in Golgi-impregnated hippocampal sections. Exposure for 2 days to hypobaric hypoxia had minimal deleterious effects on the CA1 pyramidal neurons, while exposure for 7 days resulted in a significant decrease in the number of branching points, intersections and dendritic length. Unlike the CA1 pyramidal neurons, the CA3 neurons exhibited dendritic atrophy following both 2 and 7 days of hypoxic exposure. Further, hippocampal-dependent spatial learning was affected marginally following 2 day exposure, while 7 day exposure severely affected learning of the partially baited radial arm maze task. Our study suggests that dendritic atrophy in the hippocampus on exposure to HBH could be one of the bases for the cognitive deficits exhibited under such conditions.     

Resting and active properties of pyramidal neurons in subiculum and CA1 of rat hippocampus

Action potentials are the end product of synaptic integration, a process influenced by resting and active neuronal membrane properties. Diversity in these properties contributes to specialized mechanisms of synaptic integration and action potential firing, which are likely to be of functional significance within neural circuits. In the hippocampus, the majority of subicular pyramidal neurons fire high-frequency bursts of action potentials, whereas CA1 pyramidal neurons exhibit regular spiking behavior when subjected to direct somatic current injection. Using patch-clamp recordings from morphologically identified neurons in hippocampal slices, we analyzed and compared the resting and active membrane properties of pyramidal neurons in the subiculum and CA1 regions of the hippocampus. In response to direct somatic current injection, three subicular firing types were identified (regular spiking, weak bursting, and strong bursting), while all CA1 neurons were regular spiking. Within subiculum strong bursting neurons were found preferentially further away from the CA1 subregion. Input resistance (R(N)), membrane time constant (tau(m)), and depolarizing "sag" in response to hyperpolarizing current pulses were similar in all subicular neurons, while R(N) and tau(m) were significantly larger in CA1 neurons. The first spike of all subicular neurons exhibited similar action potential properties; CA1 action potentials exhibited faster rising rates, greater amplitudes, and wider half-widths than subicular action potentials. Therefore both the resting and active properties of CA1 pyramidal neurons are distinct from those of subicular neurons, which form a related class of neurons, differing in their propensity to burst. We also found that both regular spiking subicular and CA1 neurons could be transformed into a burst firing mode by application of a low concentration of 4-aminopyridine, suggesting that in both hippocampal subfields, firing properties are regulated by a slowly inactivating, D-type potassium current. The ability of all subicular pyramidal neurons to burst strengthens the notion that they form a single neuronal class, sharing a burst generating mechanism that is stronger in some cells than others.     

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.     

Short-term exposure to an enriched environment enhances dendritic branching but not brain-derived neurotrophic factor expression in the hippocampus of rats with ventral subicular lesions

Environmental enrichment promotes structural and behavioral plasticity in the adult brain. We have evaluated the efficacy of enriched environment on the dendritic morphology and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of ventral subicular-lesioned rats. Bilateral ventral subicular lesion has significantly reduced the dendritic architecture and spine density of hippocampal pyramidal neurons. The lesioned rats exposed to enriched housing for 10 days showed a significant degree of morphological plasticity in terms of enhanced dendritic branching and spine density. However, the BDNF expression in the hippocampus remained unchanged following subicular lesion and following environmental enrichment. We suggest the participation of other neurotrophic factors in mediating the synaptic plasticity events following exposure to environmental enrichment in ventral subicular-lesioned rats.     

Electrophysiological evidence using focal flash photolysis of caged glutamate that CA1 pyramidal cells receive excitatory synaptic input from the subiculum

The hippocampus sends efferent fibers to the subiculum, which projects to the entorinal cortex. Previous studies suggest that the hippocampal CA1 area may receive a projection back from the subiculum. This hypothesis was tested using whole cell recording from CA1 pyramidal cells while subicular neurons were selectively stimulated with focal flash photolysis of caged glutamate, which avoids stimulation of fibers of passage. Control experiments showed that focal flash stimulations caused direct glutamate-mediated depolarizations and bursts of action potentials in the recorded CA1 pyramidal cells, but only when the stimulation targeted the somatodendritic regions of a neuron, not the axons. To block GABA(A)-mediated inhibition and isolate local excitatory circuits, bicuculline was applied to minislices containing only the isolated CA1 area and the subiculum. Of 24 CA1 pyramidal cells, 25% (6 of 24) consistently generated repetitive excitatory postsynaptic currents (EPSCs) in response to flash stimulation in the subiculum. The responsive neurons were located 200-500 microm from the distal end of CA1 and 400-1,100 microm from the stimulation sites in subiculum, suggesting excitatory synaptic projections from the subicular neurons to CA1 pyramidal cells. This study provides new electrophysiological evidence that CA1 pyramidal cells receive excitatory synaptic input from the subiculum. Thus a reciprocal excitatory synaptic circuit connects the subiculum and the CA1 area in the normal adult rat.     

Morphological characteristics and electrophysiological properties of CA1 pyramidal neurons in macaque monkeys

Little is known about the morphological characteristics and intrinsic electrophysiological properties of individual neurons in the nonhuman primate hippocampus. We have used intracellular recording and biocytin-labeling techniques in the in vitro hippocampal slice preparation to provide quantitative evaluation of the fundamental morphological and intrinsic electrophysiological characteristics of macaque monkey CA1 pyramidal neurons. These neurons have previously been studied in the rat in our laboratory. Monkey CA1 pyramidal neurons have an average soma volume of 3578 microm3, 4.71 basal dendrites with 53 terminal branches for a dendritic length of about 10,164 microm, 1.13 apical dendrites with 47 terminal branches for a dendritic length of about 10,678 microm. In comparison, rat CA1 pyramidal neurons have an average soma volume of 2066 microm3, 3.35 basal dendrites with 29 terminal branches for a dendritic length of about 4,586 microm, 1.43 apical dendrites with 62 terminal branches for a dendritic length of about 8,838 microm. The basic intrinsic electrophysiological properties of CA1 pyramidal cells are similar in monkeys and rats. Monkey CA1 pyramidal neurons have a resting membrane potential of about -62 mV (rat: -62 mV), an input resistance of 35 MOmega (rat: 34-49 MOmega), a rheobase of 0.17 nA (rat: 0.12-0.20 nA) and an action potential amplitude of 83 mV (rat: 71-89 mV). Although morphological differences such as the increased dendritic length may translate into differences in neural processing between primates and rodents, the functional significance of these morphological differences is not yet clear. Quantitative studies of the primate brain are critical in order to extrapolate information derived from rodent studies into better understanding of the normal and pathological function of the human hippocampus.     

Long-term study of dendritic spines from hippocampal CA1 pyramidal cells, after neuroprotective melatonin treatment following global cerebral ischemia in rats

Melatonin reduces pyramidal neuronal death in the hippocampus and prevents the impairment of place learning and memory in the Morris water maze, otherwise occurring following global cerebral ischemia. The cytoarchitectonic characteristics of the hippocampal CA1 remaining pyramidal neurons in brains of rats submitted 120 days earlier to acute global cerebral ischemia (15-min four vessel occlusion, and melatonin 10mg/(kg h 6h), i.v. or vehicle administration) were compared to those of intact control rats in order to gain information concerning the neural substrate underlying preservation of hippocampal functioning. Hippocampi were processed according to a modification of the Golgi method. Dendritic bifurcations from pyramidal neurons in both the oriens-alveus and the striatum radiatum; as well as spine density and proportions of thin, stubby, mushroom-shaped, wide, ramified, and double spines in a 50 microm length segment of an oblique dendrite branching from the apical dendrite of the hippocampal CA1 remaining pyramidal neurons were evaluated. No impregnated CA1 pyramidal neurons were found in the ischemic-vehicle-treated rats. CA1 pyramidal neurons from ischemic-melatonin-treated rats showed stick-like and less ramified dendrites than those seen in intact control neurons. In addition, lesser density of spines, lower proportional density of thin spines, and higher proportional density of mushroom spines were counted in ischemic-melatonin-treated animals than those in the sinuously branched dendrites of the intact control group. These cytoarchitectural arrangements seem to be compatible with place learning and memory functions long after ischemia and melatonin neuroprotection.     

Somal and Dendritic Development of Human CA3 Pyramidal Neurons F rom Midgestation to Middle Childhood: A Quantitative Golgi Study

The CA3 area serves a key relay on the tri‐synaptic loop of the hippocampal formation which supports multiple forms of mnemonic processing, especially spatial learning and memory. To date, morphometric data about human CA3 pyramidal neurons are relatively rare, with little information available for their pre‐ and postnatal development. Herein, we report a set of developmental trajectory data, including somal growth, dendritic elongation and branching, and spine formation, of human CA3 pyramidal neurons from midgestation stage to middle childhood. Golgi‐impregnated CA3 pyramidal neurons in fetuses at 19, 20, 26, 35, and 38 weeks of gestation (GW) and a child at 8 years of age (Y) were analyzed by Neurolucida morphometry. Somal size of the impregnated CA3 cells increased age‐dependently among the cases. The length of the apical and basal dendrites of these neurons increased between 26 GW to 38 GW, and appeared to remain stable afterward until 8 Y. Dendritic branching points increased from 26 GW to 38 GW, with that on the apical dendrites slightly reduced at 8 Y. Spine density on the apical and basal dendrites increased progressively from 26 GW to 8 Y. These data suggest that somal growth and dendritic arborization of human CA3 pyramidal neurons occur largely during the second to third trimester. Spine development and likely synaptogenesis on CA3 pyramidal cells progress during the third prenatal trimester and may continue throughout childhood. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.     

Dendritic plasticity of CA1 pyramidal neurons after transient global ischemia

Dendrites and spines undergo dynamic changes in physiological conditions, such as learning and memory, and in pathological conditions, such as Alzheimer's disease and epilepsy. Long-term dendritic plasticity has also been reported after ischemia/hypoxia, which might be compensatory effects of surviving neurons for the functional recovery after the insults. However, the dendritic changes shortly after ischemia, which might be associated with the pathogenesis of ischemic cell death, remain largely unknown. To reveal the morphological changes of ischemia-vulnerable neurons after ischemia, the present study investigated the alteration of dendritic arborization of CA1 pyramidal neurons in rats after transient cerebral ischemia using intracellular staining technique in vivo. The general appearance of dendritic arborization of CA1 neurons within 48 h after ischemia was similar to that of control neurons. However, a dramatic increase of dendritic disorientation was observed after ischemia with many basal dendrites coursed into the territory of apical dendrites and apical dendrites branched into the region of basal dendrites. In addition, a significant increase of apical dendritic length was found 24 h after ischemia. The increase of dendritic length after ischemia was mainly due to the dendritic sprouting rather than the extension of individual dendrites, which mainly occurred in the middle segment of the apical dendrites. These results reveal a plasticity change in dendritic arborization of CA1 neurons shortly after cerebral ischemia.     

Conditional dendritic spike propagation following distal synaptic activation of hippocampal CA1 pyramidal neurons

The perforant-path projection to the hippocampus forms synapses in the apical tuft of CA1 pyramidal neurons. We used computer modeling to examine the function of these distal synaptic inputs, which led to three predictions that we confirmed in experiments using rat hippocampal slices. First, activation of CA1 neurons by the perforant path is limited, a result of the long distance between these inputs and the soma. Second, activation of CA1 neurons by the perforant path depends on the generation of dendritic spikes. Third, the forward propagation of these spikes is unreliable, but can be facilitated by modest activation of Schaffer-collateral synapses in the upper apical dendrites. This 'gating' of dendritic spike propagation may be an important activation mode of CA1 pyramidal neurons, and its modulation by neurotransmitters or long-term, activity-dependent plasticity may be an important feature of dendritic integration during mnemonic processing in the hippocampus.     

Self-stimulation rewarding experience induced alterations in dendritic spine density in CA3 hippocampal and layer V motor cortical pyramidal neurons.

Self-stimulation rewarding experience induced alterations in the numerical density of spines in CA3 hippocampal and layer V motor cortical pyramidal neurons in adult male Wistar rats was evaluated. Self-stimulation experience was provided 1 h daily over a period of 10 days through stereotaxically implanted bipolar stainless steel electrodes bilaterally in lateral hypothalamus and substantia nigra-ventral tegmental area. After 10 days, rats were killed and the hippocampus and motor cortex were processed for rapid Golgi staining procedure. The dendritic spine densities were studied in CA3 hippocampal and layer V motor cortical pyramidal neurons. The spine densities were quantified in five successive segments of 15.2 microm up to a distance of 76 microm. Apical dendrites were classified as mainshaft, sub branch, oblique shaft-I, oblique shaft-II, primary branch; and basal dendrites as main shaft, primary branch and secondary branch. A grand total of 864 CA3 hippocampal and 1008 layer V motor cortical dendrites were analysed for spine counting in different groups of rats. The results revealed a significant (P<0.001; ANOVA, F-test) increase in the number of spines in all the categories of dendrites in apical and basal regions in both hippocampal and motor cortical neurons in self-stimulation group of rats. Such changes were not observed either in sham control, experimenter-administered or normal control groups of rats. The self-stimulation induced increase in the spine density suggests an increase in the postsynaptic receptive field in CA3 hippocampal and layer V motor cortical neurons. This might enhance the efficacy of synaptic transmission in these neurons. Our study clearly demonstrated the self-stimulation rewarding experience induced postsynaptic plasticity in hippocampal and motor cortical pyramidal neurons.     

Increased numerical density of synapses in CA3 region of hippocampus and molecular layer of motor cortex after self-stimulation rewarding experience.

Self-stimulation has been considered as an intensely rewarding behavioural experience, being perhaps even more influential than feeding or sexual behaviour. Our earlier studies have demonstrated a self-stimulation rewarding experience-induced increase in dendritic branching points, intersections and spine densities in CA3 hippocampal and layer V motor cortical pyramidal neurons. In the present study, we report self-stimulation-induced alterations in the numerical density of synapses in the hippocampus and motor cortex. A self-stimulation experience was provided 1 h daily for a period of 10 days through bipolar electrodes, implanted bilaterally in the lateral hypothalamus and substantia nigra-ventral tegmental area, stereotaxically. The results revealed a significant (P < 0.001) increase in the number of synapses in the CA3 region of hippocampus and the molecular layer of the motor cortex in self-stimulation-experienced rats. The increased synaptic number may be due to the activation of afferent pathways to the hippocampus and motor cortex following self-stimulation, which may lead to the induction of long-term potentiation. Long-term potentiation is known to cause structural changes by strengthening the existing synapses or resulting in the formation of new synapses. These changes may be related to the improved cognitive functions observed in self-stimulation-experienced rats.     

Effects of early environment on pyramidal neuron morphology in field CA1 of the guinea-pig

We previously demonstrated that early isolation has profound effects on the morphology of the dentate granule cells and field CA3 pyramidal neurons. Aim of the present study was to analyze the effects of early environment on the morphology of field CA1 pyramidal neurons, the third element of the hippocampal trisynaptic circuit. The dendritic trees and the soma of field CA1 pyramidal neurons were quantified in Golgi-stained brains of guinea-pigs of both sexes raised in either a social or an isolated environment.Based on the different pattern of the apical dendritic tree two major classes of CA1 pyramidal neurons were recognized (monotufted neurons and bitufted neurons). In males isolation induced in both neuron types a decrease in the number of low order apical branches but in the apical tree of the monotufted neurons isolation induced an increase in the number of intermediate order branches and dendritic length. In isolated females the apical tree of the monotufted neurons showed a very scarce atrophy. In contrast, the apical tree of the bitufted neurons from isolated females showed a decrease in the number of low and intermediate order branches and dendritic length. In isolated males the basal tree of the bitufted neurons had a large decrease in the total number of branches and dendritic length. In contrast, in isolated females the basal tree of both neuron types showed an increase in the number of low order branches. In males but not in females isolation caused a reduction in the soma dimensions of both neuron types. No isolation-induced changes were observed in dendritic spine density in either the apical or basal dendrites.The results demonstrate remarkable structural changes in CA1 pyramidal neurons following early isolation and a different reactivity to environment of the two CA1 pyramidal neuron types, their apical and basal trees and the two sexes. The neuroanatomical changes caused by isolation in field CA1 and in the two other elements of the trisynaptic circuit are likely to be associated with changes in the physiology of the hippocampal formation and in cognitive processes such as learning and memory in which the hippocampal formation plays a pivotal role.     

Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons

CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na(+) channel-mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na(+)-to-K(+) conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network.     

Estradiol increases spine density and NMDA-dependent Ca2+ transients in spines of CA1 pyramidal neurons from hippocampal slices

To investigate the physiological consequences of the increase in spine density induced by estradiol in pyramidal neurons of the hippocampus, we performed simultaneous whole cell recordings and Ca2+ imaging in CA1 neuron spines and dendrites in hippocampal slices. Four- to eight-days in vitro slice cultures were exposed to 17beta-estradiol (EST) for an additional 4- to 8-day period, and spine density was assessed by confocal microscopy of DiI-labeled CA1 pyramidal neurons. Spine density was doubled in both apical and basal dendrites of the CA1 region in EST-treated slices; consistently, a reduction in cell input resistance was observed in EST-treated CA1 neurons. Double immunofluorescence staining of presynaptic (synaptophysin) and postsynaptic (alpha-subunit of CaMKII) proteins showed an increase in synaptic density after EST treatment. The slopes of the input/output curves of both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) postsynaptic currents were steeper in EST-treated CA1 neurons, consistent with the observed increase in synapse density. To characterize NMDA-dependent synaptic currents and dendritic Ca2+ transients during Schaffer collaterals stimulation, neurons were maintained at +40 mV in the presence of nimodipine, picrotoxin, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). No differences in resting spine or dendritic Ca2+ levels were observed between control and EST-treated CA1 neurons. Intracellular Ca2+ transients during afferent stimulation exhibited a faster slope and reached higher levels in spines than in adjacent dendrites. Peak Ca2+ levels were larger in both spines and dendrites of EST-treated CA1 neurons. Ca2+ gradients between spine heads and dendrites during afferent stimulation were also larger in EST-treated neurons. Both spine and dendritic Ca2+ transients during afferent stimulation were reversibly blocked by D, L-2-amino-5-phosphonovaleric acid (D,L-APV). The increase in spine density and the enhanced NMDA-dependent Ca2+ signals in spines and dendrites induced by EST may underlie a threshold reduction for induction of NMDA-dependent synaptic plasticity in the hippocampus.     

Two different forms of long-term potentiation at CA1–subiculum synapses

Distinct functional roles in learning and memory are attributed to certain areas of the hippocampus and the parahippocampal region. The subiculum as a part of the hippocampal formation is the principal target of CA1 pyramidal cell axons and serves as an interface in the information processing between the hippocampus and the neocortex. Subicular pyramidal cells have been classified as bursting and regular firing cells. Here we report fundamental differences in long-term potentiation (LTP) between both cell types. Prolonged high-frequency stimulation induced NMDA receptor-dependent LTP in both cell types. While LTP relied on postsynaptic calcium in regular firing neurons, no increase in postsynaptic calcium was required in bursting cells. Furthermore, paired-pulse facilitation revealed that the site of LTP expression was postsynaptic in regular firing neurons, while presynaptic in burst firing neurons. Our findings on synaptic plasticity in the subiculum indicate that regular firing and bursting cells represent two functional units with distinct physiological roles in processing hippocampal output.     

Exposure to enriched environment improves spatial learning performances and enhances cell density but not choline acetyltransferase activity in the hippocampus of ventral subicular-lesioned rats

The authors demonstrated the efficacy of enriched housing conditions in promoting the behavioral recovery and neuronal survival following subicular lesion in rats. Chemical lesioning of the ventral subiculum impaired the spatial learning performances in rats. The lesion also induced a significant degree of neurodegeneration in the CA1 and CA3 areas of the hippocampus and entorhinal cortex. Exposure to enriched housing conditions improved the behavioral performance and partially attenuated the neurodegeneration in the hippocampus. The choline acetyl transferase (ChAT) activity in the hippocampus remained unchanged following ventral subicular lesion and also following exposure to an enriched environment. The study implicates the effectiveness of activity-dependent neuronal plasticity induced by environmental enrichment in adulthood following brain insult.     

Watermaze learning enhances excitability of CA1 pyramidal neurons

The dorsal hippocampus is crucial for learning the hidden-platform location in the hippocampus-dependent, spatial watermaze task. We have previously demonstrated that the postburst afterhyperpolarization (AHP) of hippocampal pyramidal neurons is reduced after acquisition of the hippocampus-dependent, temporal trace eyeblink conditioning task. We report here that the AHP and one or more of its associated currents (IAHP and/or sIAHP) are reduced in dorsal hippocampal CA1 pyramidal neurons from rats that learned the watermaze task as compared with neurons from control rats. This reduction was a learning-induced phenomenon as the AHP of CA1 neurons from rats that failed to learn the hidden-platform location was similar to that of neurons from control rats. We propose that reduction of the AHP in pyramidal neurons in regions crucial for learning is a cellular mechanism of learning that is conserved across species and tasks.     

Structural and functional abnormalities of the hippocampal formation in rats with environmentally induced reductions in prepulse inhibition of acoustic startle

The effects of social isolation on prepulse inhibition of acoustic startle (PPI), electrophysiology and morphology of subicular pyramidal neurons and the densities of interneuronal sub-types in the hippocampal formation were examined. Wistar rats (male weanlings) were housed socially (socials, n=8) or individually (isolates, n=7). When tested eight weeks later, PPI was lower in isolates. Rats then received terminal anaesthesia before slices of hippocampal formation were made in which the electrophysiological properties of a total of 108 subicular neurons were characterized. There were no differences in neuronal sub-types recorded in socials compared with isolates. Intrinsically burst-firing and regular spiking pyramidal neurons were examined in detail. There were no differences in resting membrane potential or input resistance in isolates compared with socials but action potential height was reduced and action potential threshold raised in isolates. A limited morphological examination of Neurobiotin-filled intrinsically burst-firing neurons did not reveal differences in cell-body area or in number of primary dendrites. Sections from the contralateral hemispheres of the same rats were stained with antibodies to calretinin, parvalbumin and the neuronal isoform of nitric oxide synthase (nNOS). In isolates, the density of calretinin positive neurons was increased in the dentate gyrus but unchanged in areas CA3, CA1 and subiculum. Parvalbumin and nNOS positive neuronal densities were unchanged. Hence in rats with environmentally induced reductions in PPI there are structural and functional abnormalities in the hippocampal formation. If the reduction in PPI stems from these abnormalities, and reduced PPI in rats is relevant to schizophrenia, then drugs that correct the reported electrophysiological changes might have antipsychotic effects.