Activation of pyramidal neurons by intrinsic longitudinal connections in the hippocampus

In the guinea pig, EPSPs and population spikes were found to be generated in the apical dendrites of pyramidal neurons of middle and ventral hippocampus, in response to dorsal hippocampal commissure (PSD) stimulation, without any involvement of dentate gyrus granule cells of corresponding segments. These long-latency synaptic effects were evoked only by repetitive (0.2-2.0 c/sec) PSD stimulation and showed increasing latency in ventral direction. A cross section between dorsal and middle hippocampus was followed by the disappearance of the responses ventrally to the section. The results show that the postsynaptic discharge of dorsal pyramidal neurons is transferred to more ventral hippocampal segments by an intrahippocampal longitudinal association system.     

Thin dendrites of cerebellar interneurons confer sublinear synaptic integration and a gradient of short-term plasticity

Interneurons are critical for neuronal circuit function, but how their dendritic morphologies and membrane properties influence information flow within neuronal circuits is largely unknown. We studied the spatiotemporal profile of synaptic integration and short-term plasticity in dendrites of mature cerebellar stellate cells by combining two-photon guided electrical stimulation, glutamate uncaging, electron microscopy, and modeling. Synaptic activation within thin (0.4?μm) dendrites produced somatic responses that became smaller and slower with increasing distance from the soma, sublinear subthreshold input-output relationships, and a somatodendritic gradient of short-term plasticity. Unlike most studies showing that neurons employ active dendritic mechanisms, we found that passive cable properties of thin dendrites determine the sublinear integration and plasticity gradient, which both result from large?dendritic depolarizations that reduce synaptic driving force. These integrative properties allow stellate cells to act as spatiotemporal filters of synaptic input patterns, thereby biasing their output in favor of sparse presynaptic activity.     

Ultrastructure of orexin-1 receptor immunoreactivities in the spinal cord dorsal horn

The ultrastructural properties of orexin 1-receptor-like immunoreactive (OX1R-LI) neurons in the dorsal horn of the rat spinal cord were examined using light and electron microscopy techniques. At the light microscopy level, the most heavily immunostained OX1R-LI neurons were found in the ventral horn of the spinal cord, while some immunostained profiles, including nerve fibers and small neurons, were also found in the dorsal horn. At the electron microscopy level, OX1R-LI perikarya were identified containing numerous dense-cored vesicles which were more heavily immunostained than any other organelles. Similar vesicles were also found within the axon terminals of the OX1R-LI neurons. The perikarya and dendrites of some of the OX1R-LI neurons could be seen receiving synapses from immunonegative axon terminals. These synapses were found mostly asymmetric in shape. Occasionally, some OX1R-LI axon terminals were found making synapses on dendrites that were OX1R-LI in some cases and immunonegative in others. The synapses made by OX1R-LI axon terminals were found both asymmetric and symmetric in appearance. The results provide solid morphological evidence that OX1R is transported in the dense-cored vesicles from the perikarya to axon terminals and that OX1R-LI neurons in the dorsal horn of the spinal cord have complex synaptic relationships both with other OX1R-LI neurons as well as other neuron types.     

Dendritic integration in hippocampal dentate granule cells

Hippocampal granule cells are important relay stations that transfer information from the entorhinal cortex into the hippocampus proper. This process is critically determined by the integrative properties of granule cell dendrites. However, their small diameter has so far hampered efforts to examine their properties directly. Using a combination of dual somatodendritic patch-clamp recordings and multiphoton glutamate uncaging, we now show that the integrative properties of granule cell dendrites differ substantially from other principal neurons. Due to a very strong dendritic voltage attenuation, the impact of individual synapses on granule cell output is low. At the same time, integration is linearized by voltage-dependent boosting mechanisms, only weakly affected by input synchrony, and independent of input location. These experiments establish that dentate granule cell dendritic properties are optimized for linear integration and strong attenuation of synaptic input from the entorhinal cortex, which may contribute to the sparse activity of granule cells in vivo.     

Dendrites: bug or feature?

The integrative properties of dendrites are determined by a complex mixture of factors, including their morphology, the spatio-temporal patterning of synaptic inputs, the balance of excitation and inhibition, and neuromodulatory influences, all of which interact with the many voltage-gated conductances present in the dendritic membrane. Recent efforts to grapple with this complexity have focused on identifying functional compartments in the dendritic tree, the number and size of which depend on the aspect of dendritic function being considered. We discuss how dendritic compartments and the interactions between them help to enhance the computational power of the neuron and define the rules for the induction of synaptic plasticity.     

Control of Na+ spike backpropagation by intracellular signaling in the pyramidal neuron dendrites

The integrative function of neurons depends on the somato-dendritic distribution and properties of voltage-gated ion channels. Sodium, potassium, calcium, and hyperpolarization-activated cyclic nucleotide-gated K+ (HCN) channels expressed in the dendrites can be modulated by a number of neurotransmitters and second-messenger systems. For example, activation of protein kinases leads to an increase in dendritic excitability by removing a slow inactivation of Na+ channels and decreasing the activity of transient K+ channels in the apical dendrites of hippocampal pyramidal neurons. Consequently, action potentials propagating along the dendrites can be modified significantly by a variety of neuromodulatory synaptic inputs.     

Anatomical organization of motoneurons and interneurons in the mudpuppy (Necturus maculosus) brachial spinal cord: the neural substrate for central pattern generation

The isolated brachial spinal cord of the mudpuppy is useful for studies of neural networks underlying forelimb locomotion, but information about its anatomy is scarce. We addressed this issue by combining retrograde labeling with fluorescent tracers and confocal microscopy. Remarkably, the central region of gray matter was aneural and contained only a tenuous meshwork of glial fibers and large extracellular spaces. Somata of motoneurons (MNs) and interneurons (INs), labeled retrogradely from ventral roots or axons in the ventro-lateral funiculus, respectively, were confined within a gray neuropil layer abutting the white matter borders, while their dendrites projected widely throughout the white matter. A considerable fraction of labeled INs was found contralaterally with axons crossing beneath a thick layer of ependyma surrounding the central canal. Dorsal roots (DRs) produced dense presynaptic arbors within a restricted dorsal region containing afferent terminations, within which dorsally directed MN and IN dendrites mingled with dense collections of synaptic boutons. Our data suggest that a major fraction of synaptic interactions takes place within the white matter. This study provides a detailed foundation for electrophysiological experiments aimed at elucidating the neural circuits involved in locomotor pattern generation.     

A light and electron microscopic study of the CB1 cannabinoid receptor in the primate spinal cord

The distribution of cannabinoid receptors was studied in the monkey spinal cord by immunocytochemistry and electron microscopy, using an antibody to the CB1 brain cannabinoid receptor. Large numbers of labelled neurons were observed in all portions of the grey matter of the spinal cord. These included small diameter 9–16µm neurons in the dorsal horn, larger (40–60µm) neurons in the intermediate grey, and very large (60–100µm), motor neurons in the ventral horn. Reaction product was observed in dendrites postsynaptic to unlabelled axon terminals. Since cannabinoid receptor activation decreases neuronal excitability by several mechanisms, including inhibition of voltage dependent calcium channels, the dense staining of CB1 in dorsal horn neurons suggests that CB1 could reduce calcium influx through such channels in these neurons. This, in turn, could decrease calcium-dependent changes in synaptic transmission and decrease sensitisation to nociceptive stimuli in these neurons. Similarly, the dense staining of CB1 in ventral horn cells suggests that cannabinoid receptors could limit calcium influx through voltage dependent calcium channels in these neurons, and could be significant in terms of neuroprotection to these neurons.     

离体运动神经元对腹外侧索刺激的突触反应特征

应用新片大鼠脊髓薄片运动神经元细胞内记录技术,对电刺激腹外侧索诱发的突触反应进行了电生理特性分析。结果在２８个测试的ＭＮ中,２２人有兴奋性突触后电位反应,其中２个跟随在抑制性突触反应这后,６个还对单或串刺激产生慢ＥＰＳＰ反应;ＶＬＦ－ＥＰＳＰ的潜伏期频数分布呈峰坡性偏态;同－ＭＮ的ＶＬＦ－ＥＰＳＰ与腹根ＥＰＳＰ间有典型的空间总和。     

Integrative properties of radial oblique dendrites in hippocampal CA1 pyramidal neurons

Although radial oblique dendrites are a major synaptic input site in CA1 pyramidal neurons, little is known about their integrative properties. We have used multisite two-photon glutamate uncaging to deliver different spatiotemporal input patterns to single branches while simultaneously recording the uncaging-evoked excitatory postsynaptic potentials and local Ca2+ signals. Asynchronous input patterns sum linearly in spite of the spatial clustering and produce Ca2+ signals that are mediated by NMDA receptors (NMDARs). Appropriately timed and sized input patterns ( approximately 20 inputs within approximately 6 ms) produce a supralinear summation due to the initiation of a dendritic spike. The Ca2+ signals associated with synchronous input were larger and mediated by influx through both NMDARs and voltage-gated Ca2+ channels (VGCCs). The oblique spike is a fast Na+ spike whose duration is shaped by the coincident activation of NMDAR, VGCCs, and transient K+ currents. Our results suggest that individual branches can function as single integrative compartments.     

EphA4 signaling promotes axon segregation in the developing auditory system

Precision of synaptic connections within neural circuits is essential for the accurate processing of sensory information. Specificity is exemplified at cellular and subcellular levels in the chick auditory brainstem, where nucleus magnocellularis (NM) neurons project bilaterally to nucleus laminaris (NL). Dorsal dendrites of NL neurons receive input from ipsilateral, but not contralateral, branches of NM axons whereas ventral dendrites are innervated by contralateral NM axons. This organization is analogous to that of the mammalian medial superior olive (MSO) and represents an important component of the circuitry underlying sound localization. However, the molecular mechanisms that establish segregated inputs to individual regions of NL neurons have not been identified. During synapse formation in NL, the EphA4 receptor is expressed in dorsal, but not ventral NL, neuropil, suggesting a potential role in targeting synapses to appropriate termination zones. Here, we directly tested this role by ectopically expressing EphA4 and disrupting EphA4 signaling using in ovo electroporation. We found that both misexpression of EphA4 and disruption of EphA4 signaling resulted in an increase in the number of NM axons that grow aberrantly across NL cell bodies into inappropriate regions of NL neuropil. EphA4 signaling is thus essential for targeting axons to distinct subsets of dendrites. Moreover, loss of EphA4 function resulted in morphological abnormalities of NL suggestive of errors in cell migration. These results suggest that EphA4 has multiple roles in the formation of auditory brainstem nuclei and their projections.     

Noncanonical projections to the hippocampal CA3 regulate spatial learning and memory by modulating the feedforward hippocampal trisynaptic pathway

The hippocampal formation (HF) is well documented as having a feedforward, unidirectional circuit organization termed the trisynaptic pathway. This circuit organization exists along the septotemporal axis of the HF, but the circuit connectivity across septal to temporal regions is less well described. The emergence of viral genetic mapping techniques enhances our ability to determine the detailed complexity of HF circuitry. In earlier work, we mapped a subiculum (SUB) back projection to CA1 prompted by the discovery of theta wave back propagation from the SUB to CA1 and CA3. We reason that this circuitry may represent multiple extended noncanonical pathways involving the subicular complex and hippocampal subregions CA1 and CA3. In the present study, multiple retrograde viral tracing approaches produced robust mapping results, which supports this prediction. We find significant noncanonical synaptic inputs to dorsal hippocampal CA3 from ventral CA1 (vCA1), perirhinal cortex (Prh), and the subicular complex. Thus, CA1 inputs to CA3 run opposite the trisynaptic pathway and in a temporal to septal direction. Our retrograde viral tracing results are confirmed by anterograde-directed viral mapping of projections from input mapped regions to hippocampal dorsal CA3 (dCA3). We find that genetic inactivation of the projection of vCA1 to dCA3 impairs object-related spatial learning and memory but does not modulate anxiety-related behaviors. Our data provide a circuit foundation to explore novel functional roles contributed by these noncanonical hippocampal circuit connections to hippocampal circuit dynamics and learning and memory behaviors.

This study reveals extensive non-canonical synaptic inputs to dorsal hippocampal CA3 from ventral CA1, perirhinal cortex and subicular complex, and shows that genetic inactivation of projection from ventral CA1 to dorsal CA3 impairs object-related spatial learning and memory.     

The ventral lateral geniculate nucleus,pars lateralis of the rat

Summary The synaptic organization of the pars lateralis portion of the ventral lateral geniculate nucleus is similar to that of other thalamic nuclei. There are four types of synaptic knobs (RL, RS, F1, F2). RL knobs are large and irregularly shaped, contain round synaptic vesicles and make multiple asymmetrical junctions. They are found primarily in synaptic islands making contact with gemmules, spines, small dendrites, and other synaptic profiles containing pleiomorphic synaptic vesicles (F2). Smaller RS knobs contain round vesicles and make asymmetrical junctions with the same type of elements as RL knobs, with the exception of the F2 profiles, but are seldom found in synaptic islands. F1 knobs contain flattened synaptic vesicles and form symmetrical junctions with F2 knobs, gemmules, spines, and small-medium dendrites in synaptic islands, throughout the neuropil, and on the proximal dendrites and soma of the largest type of neuron. F2 knobs are irregularly shaped, contain pleiomorphic synaptic vesicles and make symmetrical junctions primarily with gemmules and spines in synaptic islands. They are postsynaptic to RL and F1 knobs. Occipital decortication indicates that cortical terminals are of the RS type. Bilateral enucleation indicates that retinal terminals are of both the RL and RS type. The large amount of geographic overlap of retinal and cortical terminals on gemmules, spines, and small dendrites found in the neuropil outside of synaptic islands logically would maximize axonal sprouting between these two sources.We would like to thank Mr. Peter Rossetti for his excellent technical assistance on a major portion of this project, Ms. Judith Strauss for photographic assistance, and Ms. Nancy Wood for typing. Supported by grants NS 10579, NS 08724, 5 S01 RR 05402, and 2 T01 GM 00326     

Effects of active versus passive dendritic membranes on the transfer properties of a simulated neuron

In a simulated neuron with a dendritic tree, the relative effects of active and passive dendritic membranes on transfer properties were studied. The simulations were performed by means of a digital computer. The computations calculated the changes in transmembrane voltages of many compartments over time as a function of other biophysical variables. These variables were synaptic input intensity, critical firing threshold, rate of leakage of current across the membrane, and rate of longitudinal current spread between compartments. For both passive and active dendrites, the transfer properties of the soma studied for different rates of longitudinal current spread. With low rates of current spread, graded changes in firing threshold produced correspondingly graded changes in output discharge. With high rates of current spread, the neuron became a bistable operator where spiking was enhanced if the threshold was below a certain level and suppressed if the threshold was above that level. Since alterations in firing threshold were shown to have the same effect on firing rate as alterations in synaptic input intensity, the neuron can be said to change from graded to contrast-enhancing in its response to stimuli of different intensities. The presence or absence of dendritic spiking was found to have a significant effect on the integrative properties of the simulated neuron. In particular, contrast enhancement was considerably more pronounced in neurons with passive than with active dendrites in that somatic spike rates reached a higher maximum when dendrites were passive. With active dendrites, a less intense input was needed to initiate somatic spiking than with passive dendrites because a distal dendritic spike could easily propagate by means of longitudinal current spread to the soma. Once somatic spiking was initiated, though, spike rates tended to be lower with active than with passive dendrites because the soma recovered more slowly from its post-spike refractory period if it was also influenced by refractory periods in the dendrites. The experiment of comparing neurons with active and passive dendrites was repeated at a different, higher value of synaptic input. The same differences in transfer properties between the active and passive cases emerged as before. Spiking patterns in neurons with active dendrites were also affected by the time distribution of synaptic inputs. In a previous study, inputs had been random over both space and time, varying about a predetermined mean, whereas in the present study, inputs were random over space but uniform over time. When inputs were made uniform over time, spiking became more difficult to initiate and the transition from graded to bistable response became less sharp.     

The ultrastructure of the sensory cells in the chemoreceptor of the ommatophore of Helix pomatia L.

Most of the sensory cells found in the chemoreceptor of the ommatophore of Helix pomatia are typical bipolar cells. The chemoreceptor is deveded by a furrow into two parts; within the ventral subdivision the layer of sensory cell bodiesis thicker than in the dorsal part. According to the differentiations of the apical surface of the dendrites, it is possible to distinguish six different classes: a) dendrites with one cilium and 75 nm thick cytofila (sometimes dendrites of identical appearance posses more than one cilium); b)dendrites with several cilial and 150 nm thick cytofila; c) dendrites with several cilia, 50 nm thick cytofila, and long, striated rootlets; d) dendrites with several cilia bur without cytofila; e) dendrites with 130 nm thick cytofila but without cilia; and f) dendrites with 65 nm thick cytofila but without cilia; dendrites of this class are the only ones with a cytoplasm more electron dense than that of the surrounding supporting cells. All these dendrites are connected to the surrounding supporting cells by terminal bars, each consisting of zonula adhaerens, aonula intermedia and zonula septata. The perikarya of the sensory cells measure approximately 15 mum by 8 mum and enclose 10 mum by 6 mum large nuclei. Axons, originating from these perikarya, extend to the branches of the digital ganglion. In the distal part of this gangloin the axons come into synaptic contact with interneurons, but in our electron micrography it was not possible to coordinate processes and synapses with the corresponding neurons.     

Synaptic plasticity in drug reward circuitry

Drug addiction is a major public health issue worldwide. The persistence of drug craving coupled with the known recruitment of learning and memory centers in the brain has led investigators to hypothesize that the alterations in glutamatergic synaptic efficacy brought on by synaptic plasticity may play key roles in the addiction process. Here we review the present literature, examining the properties of synaptic plasticity within drug reward circuitry, and the effects that drugs of abuse have on these forms of plasticity. Interestingly, multiple forms of synaptic plasticity can be induced at glutamatergic synapses within the dorsal striatum, its ventral extension the nucleus accumbens, and the ventral tegmental area, and at least some of these forms of plasticity are regulated by behaviorally meaningful administration of cocaine and/or amphetamine. Thus, the present data suggest that regulation of synaptic plasticity in reward circuits is a tractable candidate mechanism underlying aspects of addiction.     

Insulin-like immunoreactivity in the monkey spinal cord.

Insulin-like immunoreactive neurons were localized in the cervical, thoracic, lumbar and sacral segments of the monkey spinal cord. Both dorsal and ventral horn cells were labelled. Insulin-like reaction product was localized in the cell nucleus and cytoplasm. Both inner and outer nuclear membranes were labelled. Reaction product appeared to be scattered throughout the nucleoplasm but not within the nucleolus. In the cytoplasm, labelling was mainly localized in the cisternae of rER and saccules of Golgi apparatus. Both proximal and distal dendrites were labelled, the reaction product was closely associated with the parallel arrays of neurotubules. Most of the distal dendrites were postsynaptic to non-labelled axon terminals; however, some were postsynaptic to lightly labelled axon terminals. A labelled dendrite often formed the central element of a synaptic glomerulus with several nonlabelled axon terminals. It is hypothesized that insulin-like substance(s) may be modulating nuclear activities as well as neurotransmission at the synapse.     

Neuronal control of swimming in the medicinal leech

Summary The cell bodies and function of twelve neurons whose impulse pattern is clearly related to that of the swimming rhythm were identified in the segmental ganglion of the leech. These include excitatory and inhibitory motor neurons of the dorsal and ventral longitudinal muscles and the excitatory flattener motor neuron of the dorsoventral muscles. During swimming the membrane potential of these cells oscillates between a depolarized and a hyperpolarized phase. The activity of this ensemble of cells is sufficient to account for the contractile rhythm of the swimming animal. The following connections were found between these motor neurons. Electrotonic junctions link: (1) bilaterally homologous cells; (2) excitors of the dorsal longitudinal muscles; (3) excitors of the ventral longitudinal muscles; (4) inhibitors of both dorsal and ventral longitudinal muscles. The dorsal inhibitors project via an inhibitory pathway to the dorsal excitors, and the ventral inhibitor projects via an inhibitory pathway to the ventral excitors. The membrane potential oscillation of the excitors is at least partly attributable to the phasic inhibitory synaptic input which they receive from the inhibitors. The excitatory shortener motor neuron of the entire longitudinal musculature is maintained in an inactive state during swimming. This control is achieved by rectifying electrotonic junctions linking this neuron to the dorsal and ventral excitors. These junctions allow passage of only depolarizing current from the shortener to the dorsal and ventral excitors and of only hyperpolarizing current in the reverse direction. Furthermore, both dorsal and ventral inhibitors project via inhibitory pathways to the shortener neuron.We are greatly indebted to Ann Stuart for advice and help in this study, and for communicating to us some unpublished findings. We thank Elizabeth Mullenbach for excellent technical assistance.This research was supported by grant GB 31933 X from the National Science Foundation, and by Public Health Service Research grant GM 17866 and Training Grant GM 01389 from the Institute for General Medical Sciences.     

NMDA receptor-mediated dendritic spikes and coincident signal amplification

Dendrites of cortical neurons possess active conductances, which contribute to the nonlinear processing of synaptic information. Recently it has been shown that basal dendrites can generate highly localized spikes mediated by NMDA receptor channels. These spikes may serve as a powerful mechanism to detect and amplify synchronously activated spatially clustered excitatory synaptic inputs in individual dendritic segments, and may enable parallel processing in several integrative dendritic subunits.     

Effectiveness of ascending synaptic influences from various spinal funiculi on reticulospinal neurons in cats

Activity of reticulospinal neurons evoked by stimulation of the ventral, ventrolateral, dorsolateral, and dorsal funiculi of the spinal cord was recorded extracellularly in cats anesthetized with chloralose. Responses of 57 reticulospinal neurons, of which 22 projected into the ventral funiculus, 20 into the ventrolateral, and 15 into the dorsolateral, were studied. The functional properties (conduction velocity and refractory period) and the location of the neurons of the above-mentioned groups in the medulla did not differ appreciably. The most effective synaptic activation of all neurons was observed during stimulation of the dorsal and dorsolateral funiculi. Responses to stimulation of the dorsal funiculus had the lowest threshold. These responses arose in reticulospinal neurons of the ventral and ventrolateral funiculi after the shortest latent period. The effectiveness of synaptic influences from the dorsal and dorsolateral funiculi was identical in the group of neurons of the dorsolateral funiculus. Correlation between activity evoked by stimulation of the dorsal funiculus in reticulospinal neurons and peripheral nerves indicated that the responses appeared in these cells to stimulation of muscular (groups I and II) and cutaneous (group II) afferent fibers. The results indicate that impulses from low-threshold muscular and cutaneous afferents, which effectively activate reticulospinal neurons, are transmitted along ascending pathways of the dorsal funiculi.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 11, No. 3, pp. 254–263, May–June, 1979.