Dendrites Of Hippocampal Pyramidal Neurons Research Articles

Subthreshold synaptic activation of voltage-gated Ca2+ channels mediates a localized Ca2+ influx into the dendrites of hippocampal pyramidal neurons.

1. Whole cell recordings and high-speed fluorescence imaging were used to investigate the spatial and temporal characteristics of Ca2+ influx during synaptic activity in hippocampal CA1 pyramidal neurons. Brief, subthreshold trains of synaptic potentials elicited by Schaffer collateral stimulation produced transient increases in [Ca2+]i in the apical dendrites near the site of synaptic input. The rises in [Ca2+]i were not due to Ca2+ entry through N-methyl-D-aspartate (NMDA)-activated or non-NMDA-activated glutamate channels, but were reduced by low concentrations of Ni2+. Hyperpolarizing prepulses caused an increase in the synaptically evoked Ca2+ transients, whereas strong hyperpolarization during the train prevented the rise in [Ca2+]i. The data suggest that subthreshold synaptic activity can open low-voltage-activated (T-type) Ca2+ channels and produce a local increase in intradendritic [Ca2+]. Such local increases in [Ca2+]i may be important for modulating the strength of synaptic connections.

Different Ca2+ channels in soma and dendrites of hippocampal pyramidal neurons mediate spike-induced Ca2+ influx.

1. Intracellular recordings, in conjunction with fura-2 fluorescence imaging, were used to evaluate the contribution of the different Ca2+ channel subtypes to the Ca2+ influx induced by back-propagating trains of action potentials. High-threshold channels contributed mainly to Ca2+ influx in pyramidal cell somata and proximal dendrites, whereas low-threshold and other Ni(2+)-sensitive channels played a greater role in more distal dendritic signaling. These data suggest that the different Ca2+ channel types participate in distinct physiological functions; low-threshold channels likely play a greater role in dendritic integration, whereas high-threshold channels are more important for somatic Ca(2+)-dependent processes.

Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons.

Activation of dendritic voltage-gated ion channels by local synaptic input was tested by simultaneous dendrite-attached patch-clamp recordings and whole-cell somatic voltage recordings made from CA1 pyramidal neurons in hippocampal slices. Schaffer collateral stimulation elicited subthreshold excitatory postsynaptic potentials (EPSPs) that opened voltage-gated sodium and calcium channels in the apical dendrites. The EPSP-activated sodium channels opened near the peak of the EPSP, whereas low voltage-activated calcium channels opened near the EPSP peak and during the decay phase. Dendritic high voltage-activated channels required somatic action potential generation or suprathreshold synaptic trains for activation. Dendritic voltage-gated channels are, therefore, likely to participate in dendritic integration of synaptic events.

Clustering of L-type Ca2+ channels at the base of major dendrites in hippocampal pyramidal neurons

Integration and processing of electrical signals in individual neurons depend critically on the spatial distribution of ion channels on the cell surface. In hippocampal pyramidal neurons, voltage-sensitive calcium channels have important roles in the control of Ca2(+)-dependent cellular processes such as action potential generation, neurotransmitter release, and epileptogenesis. Long-term potentiation of synaptic transmission in the hippocampal pyramidal cell, a form of neuronal plasticity that is thought to represent a cellular correlate of learning and memory, is dependent on Ca2+ entry mediated by synaptic activation of glutamate receptors that have a high affinity for NMDA (N-methyl(-D-aspartate) and are located in distal dendrites. Stimuli causing long-term potentiation at these distal synapses also cause a large local increase in cytosolic Ca2+ in the proximal regions of dendrites. This increase has been proposed to result from activation of voltage-gated Ca2+ channels. At least four types of voltage-gated Ca2+ channels, designated N, L. T and P, may be involved in these processes. Here we show that L-type Ca2+ channels, visualized using a monoclonal antibody, are located in the cell bodies and proximal dendrites of hippocampal pyramidal cells and are clustered in high density at the base of major dendrites. We suggest that these high densities of L-type Ca2+ channels may serve to mediate Ca2+ entry into the pyramidal cell body and proximal dendrites in response to summed excitatory inputs to the distal dendrites and to initiate intracellular regulatory events in the cell body in response to the same synaptic inputs that cause long-term potentiation at distal dendritic synapses.

Using genetically-defined rodent strains for the identification of hippocampal traits relevant for two-way avoidance behavior: a non-invasive approach.

Genetically-defined rodent strains permit the identification of hippocampal traits which are of functional relevance for the performance of two-way avoidance behavior. This is exemplified here by analyzing the relationship between infrapyramidal mossy fibers (a tiny projection terminating upon the basal dendrites of hippocampal pyramidal neurons) and two-way avoidance learning in about 800 animals. The necessary steps include 1) identification of structural traits sensitive to selective breeding for extremes in two-way avoidance, 2) testing the robustness of the associations found by studying individual and genetical correlations between hippocampal traits and behavior, 3) establishing causal relationships by Mendelian crossing of strains with extreme structural traits and studying the behavioral consequences of such structural 'randomization', 4) confirming causal relationships by manipulating the structural variable in inbred (isogenic) strains, thereby eliminating the possibility of genetic linkage, and 5) ruling out the possibility of spurious associations by studying the correlations between the hippocampal trait and other behaviors known to depend on hippocampal functioning. In comparison with the classical lesion approach for identifying relationships between brain and behavior, the present procedure appears to be superior in two aspects: it is non-invasive, and it focuses automatically on those brain traits which are used by natural selection to shape behaviorally-defined animal populations, i.e., it reveals the natural regulators of behavior.

μ- and δ-opioid receptor binding peaks and κ-homogeneity in the molecular layers of rat hippocampal formation

The sublaminar binding profiles of ( d-Ala-NMe-Phe-Gly-ol)-enkephalin (DAGO), (2- d-penicillamine, 5- d-penicillamine)-enkephalin (DPDPE), and dynorphin A(1–8) (DYN) were studied in the CA1 subfield and dentate gyrus of rat hippocampal formation. Binding was assayed on cryomicrotome sections using coverslip autoradiographic and single grain counting techniques. DAGO, an agonist for μ-sites, had peak binding in the stratum pyramidale with a secondary peak in the distal part of the stratum radiatum. Binding of DAGO in the dentate gyrus was homogeneous. DPDPE, a δ-site agonist, also had peak binding in the stratum pyramidale, but there was no secondary peak in the molecular layer of the hippocampus. In the dentate gyrus, DPDPE binding was highest in the inner one-third of the molecular layer immediately adjacent to the granular cell layer. The endogenous opioid DYN had a laminar binding profile that mimicked that of DAGO. However, when tritiated DYN was coincubated with unlabeled DAGO and DPDPE, as much as 90% of DYN binding was blocked and remaining binding was homogenous though a small peak remained in the stratum pyramidale. The secondary peak of DAGO binding in the stratum radiatum corresponds to an area previously determined to contain processes immunoreactive for enkephalin and gamma aminobutyric acid. This correspondence suggests that opioid compounds may mediate disinhibition of the distal dendrites of hippocampal pyramidal neurons. In addition, DYN binding patterns indicate that its action in rat hippocampus is likely by both μ- and δ-receptors.

Individual hippocampal mossy fiber distribution in mice correlates with two-way avoidance performance.

Mice systematically bred for randomization of their genotype show large individual differences when performing a two-way avoidance task (shuttle-box learning). Their behavioral scores correlate strongly (r = -0.80, P less than .01) with the number of mossy fibers synapsing on basal dendrites of hippocampal pyramidal neurons, poor avoiders having relatively more such terminals. This confirms previous findings showing that rat and mouse strains known for genetically dependent poor avoidance learning have extended intra- and infrapyramidal mossy fiber projections.

Postnatal development of the mouse dentate gyrus in organotypic cultures of the hippocampal formation.

AbstractThe hippocampal formation of newborn mice was explanted and maintained in Maximow culture assemblies for up to 35 days. At the time of explantation, only the suprapyramidal limb of the dentate gyrus was cytoarchitectonically distinct, and electron microscopy of newborn hippocampus revealed no definitive synapses. Histogenesis, as indicated by the development of the infrapyramidal limb of the dentate gyrus, and synaptogenesis, as indicated by the in vitro formation of mossy fiber synapses on the dendrites of hippocampal pyramidal neurons were studied by light and electron microscopy. At 12 days and thereafter in culture, mossy fiber terminals were found in synapsis with dendritic spines probably belonging to pyramidal cells of the hippocampal zone CA4. Near dentate granule cell somata a few axosomatic and many axospinous and axodendritic synapses were found. The data indicate that granule cells of the developing dentate gyrus are capable of differentiation in vitro into a structure essentially equivalent to that developed in vivo. The granule cells may become arranged into a recognizable granule cell layer, and develop dendritic processes which receive synapses virtually identical to those found in the intact organ. The differentiation of these features proceeds in the absence of the extrinsic afferents from the septum or from the contralateral hippocampal formation.