Postsynaptic Target Neurons Research Articles

GABAergic Excitation in the Basolateral Amygdala

GABA-containing interneurons are a diverse population of cells whose primary mode of action in the mature nervous system is inhibition of postsynaptic target neurons. Using paired recordings from parvalbumin-positive interneurons in the basolateral amygdala, we show that, in a subpopulation of interneurons, single action potentials in one interneuron evoke in the postsynaptic interneuron a monosynaptic inhibitory synaptic current, followed by a disynaptic excitatory glutamatergic synaptic current. Interneuron-evoked glutamatergic events were blocked by antagonists of either AMPA/kainate or GABA(A) receptors, and could be seen concurrently in both presynaptic and postsynaptic interneurons. These results show that single action potentials in a GABAergic interneuron can drive glutamatergic principal neurons to threshold, resulting in both feedforward and feedback excitation. In interneuron pairs that both receive glutamatergic inputs after an interneuron spike, electrical coupling and bidirectional GABAergic connections occur with a higher probability relative to other interneuron pairs. We propose that this form of GABAergic excitation provides a means for the reliable and specific recruitment of homogeneous interneuron networks in the basal amygdala.

Neuronal coherence during selective attentional processing and sensory–motor integration

Groups of neurons synchronize their activities during a variety of conditions, but whether this synchronization is functionally relevant has remained a matter of debate. Here, we survey recent findings showing that synchronization is dynamically modulated during cognitive processes. Based on this evidence, synchronization appears to reflect a general mechanism that renders interactions among selective subsets of neurons effective. We show that neuronal synchronization predicts which sensory input is processed and how efficient it is transmitted to postsynaptic target neurons during sensory–motor integration. Four lines of evidence are presented supporting the hypothesis that rhythmic neuronal synchronization, also called neuronal coherence, underlies effective and selective neuronal communication. (1) Findings from intracellular recordings strongly suggest that postsynaptic neurons are particularly sensitive to synaptic input that is synchronized in the gamma-frequency (30–90 Hz) range. (2) Neurophysiological studies in awake animals revealed enhanced rhythmic synchronization among neurons encoding task-relevant information. (3) The trial-by-trial variation in the precision of neuronal synchronization predicts part of the trial-by-trial variation in the speed of visuo-motor integration. (4) The planning and selection of specific movements can be predicted by the strength of coherent oscillations among local neuronal groups in frontal and parietal cortex. Thus, neuronal coherence appears as a neuronal substrate of an effective neuronal communication structure that dynamically links neurons into functional groups processing task-relevant information and selecting appropriate actions during attention and effective sensory–motor integration.

Differential signaling in presynaptic neurotransmitter release

Neuronal communication is tightly regulated by presynaptic signaling, thereby temporarily and locally secreting one or more transmitters in order to exert propagation or modulation of network activity. In the last 2 decades our insight into the molecular regulation of presynaptic transmitter vesicle traffic and fusion has exponentionally grown due to the identification of specific functional interactions between presynaptic proteins involved in these processes. In addition, a plethora of extracellular and intracellular messengers regulate neurotransmitter release, occasionally leading to short- or long-term adaptations of the synapse to altered environmental signals. Important in this respect is the ability of various nerve terminals to diverge their output by differentiation in secretion of co-localized transmitters. This divergence in presynaptic signaling may converge in the postsynaptic target neuron or spread to neighbouring cells. In this review differential presynaptic signaling mechanisms will be related to their potential divergent roles in transmitter release.

Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability

Mutations in several classes of embryonically-expressed transcription factor genes are associated with behavioral disorders and epilepsies. However, there is little known about how such genetic and neurodevelopmental defects lead to brain dysfunction. Here we present the characterization of an epilepsy syndrome caused by the absence of the transcription factor SOX1 in mice. In vivo electroencephalographic recordings from SOX1 mutants established a correlation between behavioral changes and cortical output that was consistent with a seizure origin in the limbic forebrain. In vitro intracellular recordings from three major forebrain regions, neocortex, hippocampus and olfactory (piriform) cortex (OC) showed that only the OC exhibits abnormal enhanced synaptic excitability and spontaneous epileptiform discharges. Furthermore, the hyperexcitability of the OC neurons was present in mutants prior to the onset of seizures but was completely absent from both the hippocampus and neocortex of the same animals. The local inhibitory GABAergic neurotransmission remained normal in the OC of SOX1-deficient brains, but there was a severe developmental deficit of OC postsynaptic target neurons, mainly GABAergic projection neurons within the olfactory tubercle and the nucleus accumbens shell. Our data show that SOX1 is essential for ventral telencephalic development and suggest that the neurodevelopmental defect disrupts local neuronal circuits leading to epilepsy in the SOX1-deficient mice.

Cooperating Synapses

In parts of the brain, such as the hippocampus, synapses are densely packed and activation of a single synapse may influence the activity of adjacent neurons, the presynaptic neuron, as well as the postsynaptic target neuron. The phenomenon by which adjacent synapses are activated, called synaptic cooperation by Arnth-Jensen et al. , has important implications, because drugs may alter this cooperative response, and this response may be an important component to the induction of long-term potentiation. Arnth-Jensen et al. used hippocampal slices and the glutamate transport inhibitor TBOA to show that when glutamate uptake was blocked, the duration of excitatory postsynaptic currents (EPSCs) was prolonged. In an experiment designed to measure charge transfer as a result of activation of N -methyl-D-aspartate (NMDA) receptor activation, they showed that extrasynaptic receptors were activated even when the glutamate uptake was fully functional. In addition to controlling the spatial activation of glutamate receptors, glutamate uptake influenced the duration of the response at a single synaptic pair under conditions of high-frequency stimulation. The implications of these results and the functional relevance of neurotransmitter spillover are discussed by Diamond. N. Arnth-Jensen, D. Jabaudon, M. Scanziani, Cooperation between independent hippocampal synapses is controlled by glutamate uptake. Nature Neurosci. 5 , 325-331 (2002). [Online Journal] J. S. Diamond, A broad view of glutamate spillover. Nature Neurosci. 5 , 291-292 (2002). [Online Journal]

Characterization of pretectal-nuclear-complex afferents to the pulvinar in the cat.

We investigated anatomical and physiological properties of the projection from the pretectal nuclear complex (PNC) to the ipsilateral lateral posterior-pulvinar complex in the cat. After Phaseolus vulgaris leucoagglutinin injections into the PNC, the majority (70%) of anterogradely labeled terminals was localized in the pulvinar proper, the remaining 30% were scattered in the lateral and medial portions of the LP. No PNC neuron retrogradely labeled from the pulvinar was found to also express glutamic acid decarboxylase (GAD) mRNA, although a large number of neurons carrying the GAD label were found in close vicinity. In contrast, 69% of retrogradely labeled PNC cells also displayed glutamate-like immunoreactivity. Twenty-six out of 96 (27%) visually responsive pulvinar neurons were orthodromically activated by electrical stimulation of the ipsilateral PNC at latencies between 1 and 10 ms (median 1.9 ms). All orthodromically activated neurons responded well to the onset and offset of large visual stimuli and to sudden stimulus shifts. Whenever a saccadic eye movement was executed, these neurons were also activated, except during saccades in darkness. The comparison of saccade-evoked response with responses to visual stimuli that elicit similar retinal image shifts revealed that pretectorecipient pulvinar neurons also seem to receive a saccade-related non-visual input. All response properties correspond to those of a specific class of pulvinar neurons that have been termed "SV" neurons because they respond to visual stimulation as well as during saccades. They also closely resemble response properties of PNC neurons that project to the ipsilateral pulvinar. The results support the proposal that PNC cells not only directly activate their postsynaptic target neurons in the pulvinar, but that they also provide a visual input to these neurons that greatly contributes to their response characteristics.

Gene expression and function of FMRFamide‐related neuropeptides in the snail Lymnaea

FMRFamide and a large family of related peptides (FaRPs) have been identified in every major metazoan phylum examined, including chordates. In the pulmonate snail Lymnaea this family of neuropeptides is encoded by a five-exon locus that is subject to alternative splicing. The two alternative mRNA transcripts are expressed in the CNS in a mutually exclusive manner at the single cell level, resulting in the differential distribution of the distinct sets of FaRPs that they encode in defined neuronal networks. Biochemical peptide purification, single-cell analysis by mass spectroscopy, and immunocytochemistry have led to an understanding of the post-translational processing patterns of the two alternative precursor proteins and identified at least 12 known and novel peptides contained in neuronal networks involved in cardiorespiration, penial control and withdrawal response. The pharmacological actions of single or co-expressed peptides are beginning to emerge for the cardiorespiratory network and its central and peripheral targets. Peptides derived from protein precursor 1 and contained in the heart excitatory central motoneurons Ehe have distinct functions and also act in concert in cardiac regulation, based on their unique effects on heartbeat and their differential stimulatory effects on second messenger pathways. Precursor-2 derived peptides, contained in the Visceral White Interneuron, a key neuron of the cardiorespiratory network, have mostly inhibitory effects on the VWI's central postsynaptic target neurons but with some of the peptides also exhibiting excitatory effects on the same cells. Microsc. Res. Tech. 49:547–556, 2000. © 2000 Wiley-Liss, Inc.

Gene expression and function of FMRFamide-related neuropeptides in the snail Lymnaea.

FMRFamide and a large family of related peptides (FaRPs) have been identified in every major metazoan phylum examined, including chordates. In the pulmonate snail Lymnaea this family of neuropeptides is encoded by a five-exon locus that is subject to alternative splicing. The two alternative mRNA transcripts are expressed in the CNS in a mutually exclusive manner at the single cell level, resulting in the differential distribution of the distinct sets of FaRPs that they encode in defined neuronal networks. Biochemical peptide purification, single-cell analysis by mass spectroscopy, and immunocytochemistry have led to an understanding of the post-translational processing patterns of the two alternative precursor proteins and identified at least 12 known and novel peptides contained in neuronal networks involved in cardiorespiration, penial control and withdrawal response. The pharmacological actions of single or co-expressed peptides are beginning to emerge for the cardiorespiratory network and its central and peripheral targets. Peptides derived from protein precursor 1 and contained in the heart excitatory central motoneurons E(he) have distinct functions and also act in concert in cardiac regulation, based on their unique effects on heartbeat and their differential stimulatory effects on second messenger pathways. Precursor-2 derived peptides, contained in the Visceral White Interneuron, a key neuron of the cardiorespiratory network, have mostly inhibitory effects on the VWI's central postsynaptic target neurons but with some of the peptides also exhibiting excitatory effects on the same cells.

Activity of foot skin mechanoreceptors and afferent nerve fibres in the adult rat sciatic nerve are altered after central axotomy of sensory neurons

The functional properties of skin mechanoreceptors were examined in the hind foot of normal rats in comparison with animals subjected to dorsal rhizotomy. Evoked nerve impulses were recorded from afferent nerve fibres of the tibial nerve. The decentralized mechanoreceptors displayed evidence of autonomous functioning, but with several abnormalities as compared to normal animals. There was a decreased sensitivity to mechanical stimulation and a lower adaptive capacity as a consequence of rhizotomy. The underlying mechanism is suggested to be a loss of central trophic support because of the interrupted link between the central nervous system and the sensory ganglion cell periphery. The findings indicate that mechanical receptors continue functioning under conditions when sensory impulses flow cannot reach postsynaptic target neurons in the central nervous system, but stop at the level of the primary sensory neuron.

Target-Specific Factors Regulate the Formation of Glutamatergic Transmitter Release Sites in Cultured Neocortical Neurons

Synapse formation in the mammalian CNS is thought to involve specific target recognition processes between presynaptic and postsynaptic neurons leading to the establishment of defined neuronal circuits. To study the role of target neuron-specific factors in synaptogenesis, we used cocultures of presynaptic explants and dissociated target neurons from rat neocortex, which enabled us to selectively vary the postsynaptic target neurons. Cocultures containing target neurons that were obtained early during development [embryonic day 16 (E16)] were compared to cocultures containing target neurons that were obtained at a later embryonic stage (E19). Postsynaptic currents (PSCs) were evoked in target neurons by maximal extracellular stimulation in the presynaptic explant. The mean amplitudes of AMPA and NMDA receptor-mediated PSCs were sixfold reduced in E16 target neurons, whereas the mean amplitudes of GABA(A) receptor-mediated PSCs did not differ between E16 and E19 target neurons. This reduction was in part caused by an apparently twofold reduction in mean quantal amplitude, as shown by recording AMPA receptor-mediated miniature PSCs. In addition, a reduced number of glutamatergic release sites in E16 target neurons was revealed by synapsin I immunostaining of dendritic presynaptic terminals. No differences in mean release probability were observed between E16 and E19 target neurons. Thus, the formation of glutamatergic transmitter release sites was strongly influenced by target neuron-specific factors. The formation of functional GABAergic synapses, however, was independent of the type of target neurons, suggesting specific retrograde signaling during the establishment of glutamatergic synapses.

Diverse effects of Purkinje cell loss on deep cerebellar and vestibular nuclei neurons in Purkinje cell degeneration mutant mice: A possible compensatory mechanism

The genetic defect in the Purkinje cell degeneration (PCD) mutant mouse completely disrupts the cerebellar corticonuclear connection through intrinsic action on the final integrating unit of the cerebellar cortex, the Purkinje cell (PC). The postsynaptic target neurons of the PC in the deep cerebellar nuclei (DCN) and the vestibular nuclei (VN) are denervated by this PC loss by more than two-thirds of their total y-aminobutyric acid (GABA)-ergic innervation. This massive disinhibition should be reflected in an increased and thus electrophysiologically detectable activity of the respective neurons. To address this question, we performed extracellular recordings of PCD mutant and corresponding wild-type VN neurons under sinusoidal vestibular stimulation. The response amplitudes (neuronal response to sinusoidal rotation) of VN neurons in PCD mutant mice showed a decrease rather than the expected increase. The same was true for the mean resting rate, whereas the phase relationships were unaffected for the most part. This finding is a clear indication of compensatory reactions in the VN that substitute quantitatively for the lost PC inhibition. The expression of the calcium-binding protein parvalbumin (Parv) is assumed to correlate with the physiological activity of neurons, and Parv is localized predominantly in inhibitory neurons. Because inhibitory inter- or projecting neurons are also largely denervated by the PC loss, Parv immunocytochemistry also was performed. In wild-type mice, only very few Parv-immunopositive (Parv+) somata were present in the VN, and none were present in the DCN. In PCD mutant mice, a substantial number of Parv+ neuronal somata were visible in the VN, and even more were visible in the DCN. This increase in Parv+ somata in PCD mutant mice is closely related temporally and spatially to the extent of denervation caused by the PCD. Parv+ neuronal somata are first visible in the dentate nucleus at postnatal day (P) 24 and appear in the other cerebellar and VN up to P29. Direct double labeling of Parv and GABA and of Parv and glycine reveals that the large majority of Parv + neurons colocalize GABA, glycine, or both inhibitory transmitters. These results show that neurons that are postsynaptic to cerebellar PC develop diverse physiological and biochemical reactions in the course of genetically determined PCD. These mechanisms are likely to contribute to the phenotypically mild motor disturbances observed in PCD mutant mice.

Enhancement of whole cell synaptic currents by low osmolarity and by low [NaCl] in rat hippocampal slices.

We recorded whole cell currents of patch-clamped neurons in stratum pyramidale of CA1 region of rat hippocampal tissue slices. Synaptic currents were evoked by orthodromic stimulation while holding potential of the neuron was varied from hyperpolarized to depolarized levels. Extracellular osmolarity (pi(o)) was lowered by superfusion with artificial cerebrospinal fluid in which NaCl concentration ([NaCl]) was reduced. The effect of low extracellular NaCl was tested in additional trials in which NaCl was substituted by isosmolar fructose. Both lowering of pi(o) and isosmotic lowering of extracellular [NaCl] ([NaCl]o) caused reversible increase of excitatory postsynaptic currents. The effect of lowering pi(o) was concentration dependent, and it was significantly stronger than the effect of equivalent isosmotic lowering of [NaCl]o. Inhibitory postsynaptic currents also increased in many but not in all cases. Lowering of pi(o) caused a prolongation of the time constant of relaxation of the capacitive charging current induced by small hyperpolarizing voltage steps. A virtual input capacitance, calculated by dividing this time constant by the input resistance, increased during hypotonic exposure. Isosmotic lowering of [NaCl]o had no effect on time constant or input capacitance. Depolarizing voltage commands evoked spikelike inward currents presumably representing Na+-dependent action potentials generated outside the voltage-clamped region of the cell. These current spikes became smaller in low pi(o) and in low [NaCl]o. Broader, voltage-dependent, presumably Ca2+-mediated inward currents became more prominent during hypotonic exposure. We conclude that lowering of [NaCl]o causes enhancement of excitatory synaptic transmission. Transmission may be facilitated by the uptake of Ca2+ into presynaptic terminals as well as into postsynaptic target neurons, induced by the low [NaCl]o. Lowering of pi(o) enhances synaptic transmission more than does a corresponding isosmotic lowering of [NaCl]. The excess increase recorded from the cell soma in low pi(o) may in part be due to changing electrotonic length caused by the swelling of dendrites.

Activation of pharmacologically distinct metabotropic glutamate receptors depresses reticulospinal-evoked monosynaptic EPSPs in the lamprey spinal cord.

1. Different metabotropic glutamate receptors (mGluRs) can modulate synaptic transmission in different regions in the CNS, but their roles at individual synaptic connections have not been detailed. We used paired intracellular recordings from reticulospinal axons and their postsynaptic target neurons in the lamprey spinal cord to investigate the effects of mGluR activation on glutamatergic synaptic transmission. 2. The mGluR agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxyylic acid [(1S,3R)-ACPD] and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) both reduced the amplitude of monosynaptic excitatory postsynaptic potentials (EPSPs) elicited by stimulation of single reticulospinal axons. The depression of monosynaptic unitary EPSPs occurred without any apparent change in the input resistance of postsynaptic neurons. Furthermore, the mGluR agonists did not affect the amplitude of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced depolarizations. Taken together, these results thus suggest that (1S,3R)-ACPD and L-AP4 depress reticulospinal synaptic transmission via presynaptic mechanisms. 3. (2S,1'S,2'S)-2-(carboxycyclopropyl) glycine (L-CCG-I), which selectively activates group II mGluRs, also reduced the amplitude of reticulospinal-evoked EPSPs without any apparent change in the input resistance or membrane potential of the postsynaptic neuron. 4. The mGluR antagonist alpha-methyl-L-AP4 blocked the depression induced by L-AP4 but not that induced by (1S,3R)-ACPD. Furthermore, the effects of coapplication of (1S,3R)-ACPD and L-AP4 were additive, suggesting that they inhibit synaptic transmission by an action on pharmacologically distinct mGluRs. 5. These results provide evidence for the colocalization of at least two different subtypes of presynaptic mGluRs on a single reticulospinal axon in the lamprey. These presynaptic mGluRs could serve as glutamatergic autoreceptors limiting the extent of reticulospinal-mediated excitation of spinal neurons.

Electrophysiology and GABA-immunocytochemistry in the vestibular nuclei of normal (C57BL/6J) and Leaner mutant mice

Neurological disorders of genetic origin that lead to distinct disarrangements of the cerebellar wiring and cause a specific motor behaviour are likely to differentially influence the response properties and activity of postsynaptic cerebellar target neurons in the deep cerebellar (DCN) and vestibular nuclei (VN). Comparative electrophysiological and morphological analyses of these neurons in different mutants may increase our understanding of the physiological consequences of cell damage to the cerebellum and help to elucidate the relationships between histopathology and severeness of motor impairment. The Leaner mutation removes GABAergic inhibitory input to the VN predominantly originating from Purkinje cells (PC) located in the anterior lobe of the cerebellum and causes extremely severe motor disability when compared to other cerebellar mutants. In the present study the electrophysiological properties of naturally stimulated (sinusoidal head and body rotation) neurons in the VN of Leaner mutants and their corresponding wild-types (C57BL/6J) were investigated. Neuronal activity of VN single units in Leaner mutants is significantly increased over that of wild-types (frequency range 0.2-0.6 Hz) and more pronounced for type I neurons than for type II. Phase relationships and spontaneous activity are similar at these frequencies in both groups. To elucidate the degree of GABAergic input loss on VN-neurons, quantitative morphometric and numerical analyses of GABA-immunopositive synaptic boutons in the lateral VN of Leaner mutants were performed in addition and revealed significantly smaller terminals and a massive decrease (80%) in Leaner mutant terminal numbers compared to controls. In the context of the findings recently obtained in Weaver and Purkinje cell degeneration (PCD) mutants, the results in Leaner suggest that the loss of inhibition due to the PC'. degeneration in the anterior vermis leads to a differential enhancement of type I and type II target neuron activity in the VN. The overall. activity in Leaner is intermediate between PCD (no increase in activity and Weaver (strong increase of type I but no increase of type [I). GABA-immunocytochemistry supports the idea that in Leaner the lost GABAergic PC-innervation of the lateral VN has not been replaced by surviving PCs, which is in contrast to Weaver where sprouting of GABAergic terminals in this nucleus was observed. Substitution of lost cerebellar inhibition by non-cerebellar sources, as suggested in the case of PCD-mutants, is uncertain in Leaner due to the increased activity of type I target neurons. These conditions may contribute, among others, to the severe motor disturbances in Leaner.

Plasticity of complex terminals in lamina II in partially deafferented spinal cord: The cat spared root preparation

Projections to the dorsal horn change in adult mammals in response to complete or partial deafferentation. The number of synaptic terminals remains constant after complete lumbosacral deafferentation, indicating replacement of lost dorsal root terminals by newly formed terminals from spared intrinsic systems. The density of a spared central projection of a dorsal root is increased in dorsal horn after partial deafferentation, consistent with sprouting by the axons in the spared root. In this study, we have used electron microscopy to study morphological changes in a specific class of terminals in the dorsal horn induced by partial deafferentation. Complex terminals (CTs) in the dorsal horn originate exclusively from dorsal roots and are readily distinguished morphologically. The CTs and the postsynaptic densities (PSDs) associated with CTs were measured in lamina II at L5 and L6 in cats subjected to unilateral spared root (L6) dorsal rhizotomies and compared to CTs in the control side. Acutely following partial deafferentation, the number of CT profiles decreased. At more chronic survivals, the number of CT profiles were restored to normal levels, and both the number and the length of PSDs were increased. The changes in CTs and PSDs suggest sprouting and synaptogenesis by the spared dorsal root fibers that produce changes in the postsynaptic neuron. Spared root deafferentation thus elicits compensatory changes in presynaptic terminals of the spared root and also in their postsynaptic target neurons.

Activity-dependent remodeling of connections in the mammalian visual system

The development of precise connections in the mammalian central nervous system requires neural activity. Synchronous patterns of afferent activity, and coincident afferent and target activity are required for specifying the neuronal connectivity that characterizes the adult visual pathway in mammals. During development, postsynaptic target neurons communicate with presynaptic afferents. Recent evidence suggests that the mechanisms that underlie activity-dependent development of connections in the visual system may share significant similarities with the mechanisms responsible for synaptic plasticity in the adult brain.

Fine structural alteration in target-deprived axonal terminals in the rat thalamus

Lesioning of thalamic target neurons in the adult rat provokes a resorption of terminal axonal branches of afferent neurons from the dorsal column nuclei. There is, however, no massive neuronal loss in the dorsal column nuclei. In the adult, therefore, the thalamic post synaptic target cells influence primarily the extent of the terminal component of the afferent neurons. The subcellular changes underlying the regression of these adult terminals are unknown. To address this issue, we have looked at the electron microscopic level for the ultrastructural correlates of this retraction of the terminal compartment of target-deprived neurons in the adult rat thalamus. By analysing the fine structure of target-deprived axons and their immunoreactivity for a specific synaptic protein, synaptophysin, we have observed that all the organelles and the protein formed in the cell body, including dense-core vesicles, continue to be transported to the terminal compartment and accumulate at this level. At the terminal level, engorgement of organelles induces the formation of varicosities. An enormous increase in local degradative activity occurs in parallel to this accumulation. In contrast, organelles involved in membrane turnover and degradation (including synaptic and coated vesicles, multivesicular bodies, lysosomes) in the nerve terminals are clearly modified. There is a progressive loss of synaptic vesicles, whereas clathrin-coated vesicles and multivesicular bodies are numerous. We propose that the resorption of terminal axonal branches after thalamic target deprivation in the adult is associated with a bias of the system of membrane recycling at the axonal terminals towards degradation. In the absence of apparent changes in the pathways originating from the cell body in these conditions, it is unlikely that presynaptic neurons in the adult thalamus are dependent upon post synaptic target neurons for the delivery of organelles and proteins to the terminals.

Dynamics of synaptic vesicle fusion and membrane retrieval in synaptic terminals.

Communication among neurons occurs at specialized synaptic junctions, where neurotransmitter is released via calcium-dependent exocytosis from the synaptic terminal of the presynaptic cell onto the postsynaptic target neuron. Here we exploit the unique properties of giant synaptic terminals of bipolar neurons from goldfish retina to establish the kinetics and calcium-dependence of exocytosis, and the characteristics of membrane retrieval following secretion in presynaptic terminals. Simultaneous patch-clamp, calcium-indicator dye and time-resolved capacitance measurements reveal that activation of calcium current drives secretion at a rapid rate of about 10,000 vesicles per s and the calcium level necessary to drive secretion is locally greater than 50 microM. Two components of membrane retrieval were observed following secretory stimulation. After strong stimulation, capacitance returned to rest with a time constant of about 30 s, but after weaker stimuli recovery was much faster, with a time constant of about 2 s. Secretion in a vertebrate central nervous system neuron was thus found to differ substantially from that in other secretory cells in its rapid rate of vesicle fusion, requirement for high levels of intracellular calcium, and the high speed and completeness of membrane retrieval. These distinctive features reflect the specialization of neuronal synaptic terminals for rapid and focally directed release of neurotransmitter.

Electrical coupling of mechanoreceptor afferents in the crayfish: a possible mechanism for enhancement of sensory signal transmission.

1. Central electrical coupling between primary afferent axons was investigated in an in vitro preparation of the crayfish thoracic locomotor system by using intracellular recordings. 2. Intracellular injection of the dye Lucifer yellow in single afferents resulted in staining of one to three additional afferents through dye-coupling. Three-dimensional confocal imaging of dye-coupled axons revealed a large zone of close apposition that may correspond to the gap junction site. 3. A depolarization preceding the spike in one sensory terminal was shown to facilitate the excitatory postsynaptic potential occurring in postsynaptic motoneurons. Further, a spike in one afferent axon can depolarize other, electrically coupled, axons above spike threshold, resulting in an increased number of active afferents. 4. The electrical coupling occurred between sensory afferents of similar function. It may therefore serve to facilitate sensory signal transmission from functionally homologous afferents onto postsynaptic target neurons.

Atrophy and Degeneration of Ganglion Cells in Central Retina Following Loss of Postsynaptic Target Neurons in the Dorsal Lateral Geniculate Nucleus of the Adult Cat

Selective degeneration of neurons in the dorsal lateral geniculate nucleus (dLGN) of the adult cat was produced by in situ injection of kainic acid. This rapid degeneration mimics the loss of lateral geniculate neurons seen after neonatal visual cortex ablation. Following survivals of 2, 4, or 6 months, the geniculate was injected with horseradish peroxidase (HRP) and the retinas were examined for the presence of retrogradely labeled, as well as unlabeled, cells. Total ganglion cell density in central nasal retina was not different from that of controls at 2 or 4 months, but by 6 months had decreased to 68% of control values. The proportion of cells labeled with HRP did not change at 2 months, but decreased from 84% in controls to less than 1% by 4 months, and none were labeled at 6 months. Surviving ganglion cells in central retina showed atrophy of the cell body, a finding not apparent in data from the retinal periphery. Shrinkage occurred in the few cells labeled with HRP surviving at 4 months, as well as among the unlabeled cells surviving at 4 and 6 months. These results show that the survival of central retinal ganglion cells in the cat continues to depend on intact target neurons beyond the period of development. Mature ganglion cells in central retina respond to loss of appropriate targets first by axon terminal retraction and then by atrophy and cell death. However, when compared to the response of cells located in far peripheral retina following dLGN neuron loss, central ganglion cells take longer to undergo axonal retraction and a greater proportion of the central ganglion cells, although atrophied, survive after 6 months.