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Transneuronal transfer of herpes virus from peripheral nerves to cortex and brainstem.

The transneuronal transfer of neurotropic viruses may represent an effective tool for tracing chains of connected neurons because replication of virus in the recipient neurons after transfer amplifies the "tracer signal." Herpes simplex virus type 1 was transferred transneuronally from forelimb and hindlimb nerves of rats to the cortical and brainstem neurons that project to the spinal enlargements to which the nerves receiving injections are connected. This transneuronal transfer of herpes simplex virus type 1 from peripheral nerves has the potential to be used to identify neurons in the brain that are related transsynaptically to different nerves and muscles.

Animals↗

Dynamic behavior of a neural network model of locomotor control in the lamprey.

1. Experimental studies have shown that a central pattern generator in the spinal cord of the lamprey can produce the basic rhythm for locomotion. This pattern generator interacts with the reticular neurons forming a spinoreticulospinal loop. To better understand and investigate the mechanisms for locomotor pattern generation in the lamprey, we examine the dynamic behavior of a simplified neural network model representing a unit spinal pattern generator (uPG) and its interaction with the reticular system. We use the techniques of bifurcation analysis and specifically examine the effects on the dynamic behavior of the system of 1) changing tonic drives to the different neurons of the uPG; 2) altering inhibitory and excitatory interconnection strengths among the uPG neurons; and 3) feedforward-feedback interactions between the uPG and the reticular neurons. 2. The model analyzed is a qualitative left-right symmetric network based on proposed functional architecture with one class of phasic reticular neurons and three classes of uPG neurons: excitatory (E), lateral (L), and crossed (C) interneurons. In the model each class is represented by one left and one right neuron. Each neuron has basic passive properties akin to biophysical neurons and receives tonic synaptic drive and weighted synaptic input from other connecting neurons. The neuron's output as a function of voltage is given by a nonlinear function with a strict threshold and saturation. 3. With an appropriate set of parameter values, the voltage of each neuron can oscillate periodically with phase relationships among the different neurons that are qualitatively similar to those observed experimentally. The uPG alone can also oscillate, as observed experimentally in isolated lamprey spinal cords. Varying the parameters can, however, profoundly change the state of the system via different kinds of bifurcations. Change in a single parameter can move the system from nonoscillatory to oscillatory states via different kinds of bifurcations. For some parameter values the system can also exhibit multistable behavior (e.g., an oscillatory state and a nonoscillatory state). The analysis also shows us how the amplitudes of the oscillations vary and the periods of limit cycles change as different bifurcation points are approached. 4. Altering tonic drive to just one class of uPG neurons (without altering the interconnections) can change the state of the system by altering the stability of fixed points, converting fixed points to oscillations, single oscillations to two stable oscillations, etc. Two-parameter bifurcation diagrams show the critical regions in which a balance between the tonic drives is necessary to maintain stable oscillations. A minimum tonic drive is necessary to obtain stable oscillatory output. With appropriate changes in the tonic drives to the L and C neurons, stable oscillatory output can be obtained even after eliminating the E neurons. Indeed, the presence of active E neurons in the biological system does not prove they play a functional role in the system, because tonic drive from other sources can substitute for them. On the other hand, very high excitation of any one class of neurons can terminate oscillations. Appropriate balance of tonic drives to different neuron classes can help sustain stable oscillations for larger tonic drives. Published experimental results concerning changes in amplitude and swimming frequency with increased tonic drives are mimicked by the model's responses to increased tonic drive. 5. Interconnectivity among the neurons plays a crucial role. The analysis indicates that the C and L classes of neurons are essential components of the model network. Sufficient inhibition from the L to C neurons as well as mutual inhibition between the left and right halves is necessary to obtain stable oscillatory output. When the E neurons are present in the model network, they must receive appropriate tonic drive and provide appropriate excitation

Animals↗

Dissecting Nck/Dock signaling pathways in Drosophila visual system.

The establishment of neuronal connections during embryonic development requires the precise guidance and targeting of the neuronal growth cone, an expanded cellular structure at the leading tip of a growing axon. The growth cone contains sophisticated signaling systems that allow the rapid communication between guidance receptors and the actin cytoskeleton in generating directed motility. Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter protein in photoreceptor (R cell) axon guidance and target recognition in the Drosophila visual system, suggesting strongly that Nck/Dock is one of the long-sought missing links between cell surface receptors and the actin cytoskeleton. In this review, I discuss the recent progress on dissecting the Nck/Dock signaling pathways in R-cell growth cones. These studies have identified additional key components of the Nck/Dock signaling pathways for linking the receptor signaling to the remodeling of the actin cytoskeleton in controlling growth-cone motility.

Actins↗

Presynaptic frequency- and pattern-dependent filtering.

Dual intracellular recordings from pairs of synaptically connected neurones have demonstrated that the frequency-dependent pattern of transmitter release varies dramatically between different classes of connections. Somewhat surprisingly, these patterns are not determined by the class of neurone supplying the axon alone, but to a large degree by the class of postsynaptic neurone. A wide range of presynaptic mechanisms, some that depress the release of transmitter and others that enhance release have been identified. It is the selective expression of these different mechanisms that determines the unique frequency- and pattern-dependent properties of each class of connection. Although the molecular interactions underlying these several mechanisms have yet to be fully identified, the wealth and complexity of the protein-protein and protein-lipid interactions that have been shown to control the release of transmitter suggest many ways in which the properties of a synapse may be tuned to respond to particular patterns and frequencies.

Animals↗

Specification of layer-specific connections in the developing cortex.

One of the basic tasks of neurobiology is to understand how the precision and specificity of neuronal connections is achieved during development. In this paper we reviewed some recent in vitro studies on the developing mammalian cerebral cortex that have been made towards this end. The results of these experiments provided evidence that membrane-associated molecules are instrumental for the formation of specific afferent and efferent cortical projections. Substrate-bound molecules guide growing axons towards their target, regulate the timing of thalamocortical innervation and mediate target cell recognition. Moreover, a newly described glycoprotein, defined by a monoclonal antibody, revealed a molecular heterogeneity in the developing white matter. Since this molecule has opposite effects on thalamic and cortical axons, it might play a role in the segregation of axons running to and from the cortex. Substrate-bound cues are important during the formation of local cortical circuits. In vitro assays demonstrated that molecular components confined to individual cortical layers control the laminar specificity of cortical axon branching. This suggests that similar developmental strategies contribute to the laminar specification of extrinsic and intrinsic cortical circuits. Thus substrate-bound molecules might provide the framework for subsequent activity-dependent mechanisms that control the elaboration of precise connections between the cortical columns. A major challenge ahead is to identify the factors that mediate these processes and to determine their mode of action. Recently, two families of proteins, the netrins and the semaphorins/collapsins, have been identified as growth cone signals in the developing spinal cord (reviewed in Goodman, 1994; Colamarino and Tessier-Lavigne, 1995a; Dodd and Schuchardt, 1995; Kennedy and Tessier-Lavigne, 1995). Semaphorins/collapsins appear to regulate axonal guidance by repelling growth cones and by inhibiting axonal branching and synapse formation. Originally, netrins have been purified as diffusible chemoattractants for commissural axons of the dorsal spinal cord, but it is now well established that they can also function as chemorepellent factors for other classes of neurons. Since netrins are related to extracellular matrix components and since they can bind to the cell surface, they might also act as local guidance cues. A possible role of netrins and semaphorins/collapsins in the development of cortical connections is likely to be resolved in the near future. The identification of the factors that regulate specific branching patterns of cortical neurons might provide a better understanding of cortical development, but it might also be relevant to some aspects of plasticity and repair in the adult cortex.

Afferent Pathways↗

Single neuron mosaics of the drosophila gigas mutant project beyond normal targets and modify behavior.

gigas is a lethal mutant that differentiates enlarged cells, including the nucleus. This trait manifests only after the completion of the mitotic program. We have taken advantage of this phenotype to test in vivo the capacity of normal target cells to arrest the growth of mutant sensory axons. Single neuron connectivity changes have been analyzed in mosaics after horseradish peroxidase retrograde tracings. A mutant mechanoreceptor neuron, growing over a genetically normal substrate, contacts its normal target, and in addition projects to novel areas of the CNS. The mutant axon does terminate its growth eventually, and the new additional targets that are reached correspond to mechanoreceptor domains in other ganglia, indicating that this territorial constraint is operational in the mutant. gigas neurons maintain their stereotyped profile and represent an expanded version of the normal branching pattern. The ultrastructure of the invading projections does not reveal gliotic or necrotic reactions from the new cell contacts. The functional consequences of the connectivity changes produced by the mutant mechanoreceptors have been studied in grooming behavior. Mosaic flies carrying a single gigas mechanoreceptor show modified, albeit context-coherent, grooming responses after stimulation of the mutant bristle, whereas the response from neighboring normal sensory neurons remains unchanged. All of these experiments indicate that target recognition and growth arrest are two dissectible processes of neural development, and they highlight the autonomous features of the growth cone during pathfinding.

Animals↗

Growth of cortical neuronal network in vitro: modeling and analysis.

We present a detailed analysis and theoretical growth models to account for recent experimental data on the growth of cortical neuronal networks in vitro [Phys. Rev. Lett. 93, 088101 (2004)]. The experimentally observed synchronized firing frequency of a well-connected neuronal network is shown to be proportional to the mean network connectivity. The growth of the network is consistent with the model of an early enhanced growth of connection, but followed by a retarded growth once the synchronized cluster is formed. Microscopic models with dominant excluded volume interactions are consistent with the observed exponential decay of the mean connection probability as a function of the mean network connectivity. The biological implications of the growth model are also discussed.

Action Potentials↗

Neuroarchitecture of the central complex in the brain of the locust Schistocerca gregaria and S. americana as revealed by serotonin immunocytochemistry.

The central complex is a prominent structure in the insect brain, yet its anatomical organization and functional role is still poorly understood. To facilitate investigations on the physiology of the central complex, this study describes its anatomical organization in the brain of locusts (Schistocerca gregaria and Schistocerca americana) based on an investigation of serotonin immunocytochemistry. Most subdivisions of the central complex including the protocerebral bridge, several layers in the upper division of the central body, and the noduli of the central body are innervated by serotonin-immunoreactive neurons, while the lower division of the central body does not exhibit serotonin-like immunoreactivity. Several types of serotonin-immunoreactive neurons can be distinguished. A system of about 60 columnar neurons innervates the protocerebral bridge, layer III of the upper division of the central body, and the noduli. A group of 15-20 bilateral pairs of serotonin-immunoreactive neurons connects the posterior optic tubercles with the protocerebral bridge. About ten pairs of neurons with somata in the inferior protocerebrum innervate layer Ia of the upper division of the central body. In addition, large-field neurons arborize in layers Ia and Ib of the upper division of the central body and in the lateral accessory lobes. The detailed mapping of serotonin immunoreactivity provides further insight into the anatomical organization of the central complex and suggests that serotonin is a major neuroactive substance within this brain structure.

Africa↗

Integrating bits and pieces: synapse structure and formation in Drosophila embryos.

During the development of the nervous system, numerous neurons connect to form complex networks. In order to build a functional network each neuron has to establish contacts with appropriate target cells, and at these contacts synapses of the right quality and strength have to be formed. Gaining insight into the mechanisms underlying this complex development is an important step towards a better understanding of how the nervous system is formed and behaviour generated. One model system in which synapse formation can be studied at the morphological, physiological and molecular level is that of the fruitfly Drosophila, and insights gained from Drosophila embryos are reviewed here. The first part of this review deals with the neuromuscular junction as the best-known synaptic contact in Drosophila. It describes: (1) its structure, (2) mechanisms underlying the formation of the neuromuscular cell junction and the arborisation of the presynaptic terminal, and (3) our present understanding of signal-dependent and -independent processes during synapse formation at the neuromuscular junction. The last part of this review deals with the question of how particular neurons can adopt specific synaptic properties, stating as an example the development of the neural lineage of NB7-3, which gives rise to two serotonergic neurons.

Animals↗

Estrogen effects on neuronal responsiveness to electrical and neurotransmitter stimulation: an in vitro study on the ventromedial nucleus of the hypothalamus.

To investigate the effects of estrogen on the activity of the neurons in the hypothalamic ventromedial nucleus (VMN), the single-unit activity was recorded from in vitro brain tissue slices prepared from ovariectomized rats that were either treated or untreated with estrogen. In tissue slices continuously perifused with estrogen-free solution, half of the 348 VMN neurons studied were silent or nearly silent, and the rest fired spontaneously at low rates. Electrical stimulation of the periventricular region medial to the VMN evoked not only 3 types of orthodromic responses, but also antidromic responses from many VMN neurons, indicating that the VMN and the periventricular region are intimately and reciprocally connected. Neuronal responses to a battery of 6 neurotransmitters were studied by microinjecting 50 microliters of a transmitter solution directly into the chamber where the tissue slice was being continuously perifused. When effective, glutamate (Glut) was almost exclusively excitatory; acetylcholine (ACh) and norepinephrine (NE) could be excitatory and/or inhibitory; 5-hydroxytryptamine (5-HT) and dopamine (DA) were predominantly inhibitory; and gamma-amino-butyric acid (GABA) was exclusively inhibitory on neuronal activity. The overall resting neuronal activity and responses to the transmitter were very similar to those observed in in vivo studies, indicating that, for VMN at least, in vitro tissue slices can serve as a simplified model for studying neuronal activity and responses. Comparisons of results between estrogen-treated and untreated preparations showed that chronic, in vivo estrogen treatments, while having no effect on resting firing rate, selectively facilitated the responsiveness of silent (but not spontaneously active) neurons to excitatory orthodromic inputs, and the responsiveness to the excitatory action of ACh, the overall action of NE and the inhibitory action of 5-HT. These selective estrogen effects would no doubt alter the input-output relationships of VMN neurons evoked by the orthodromic inputs and ACh, NE and 5-HT. Since the VMN is crucial to many biological functions, and the cholinergic, adrenergic and serotonergic inputs to the ventromedial hypothalamus are involved in the estrogenic regulation of sexual behavior, reproductive neuroendocrine, and other biological functions, the alteration of the input-output relationships evoked by the orthodromic and transmitter inputs would affect the regulation of many functions.

Acetylcholine↗

Serotonin-immunoreactive neurones in the visual system of the praying mantis: an immunohistochemical, confocal laser scanning and electron microscopic study.

The distribution, number, and morphology of serotonin-immunoreactive (5-HTi) neurones in the optic lobe of the praying mantis Tenodera sinensis were studied using conventional microscopy and confocal laser scanning microscopy. Five or six 5-HTi neurones connect the lobula complex with the medulla, and at least 50 5-HTi neurones appear to be confined to the medulla. In addition, a few large 5-HTi processes from the protocerebrum supply the lobula complex, and two large 5-HTi processes from the protocerebrum ramify in the medulla and lamina, where they show wide field arborisations. In order to provide a basis for understanding the action of serotonin in the lamina, the ultrastructure of its 5-HTi terminals was examined by conventional and immunohistochemical electron microscopy. The 5-HTi profiles were filled with dense core vesicles and made synapses. Output synapses from 5-HTi profiles outnumbered inputs by about 3 to 1. The terminals of the 5-HTi neurones were in close contact with cells of various types, including large monopolar cells, but close apposition to photoreceptor terminals was rare, and no synapses were found between 5-HTi terminals and photoreceptor terminals.

Anatomy, Artistic↗

Muscimol-induced death of GABAergic neurons in rat brain aggregating cell cultures.

During brain development, spontaneous neuronal activity has been shown to play a crucial role in the maturation of neuronal circuitries. Activity-related signals may cause selective neuronal cell death and/or rearrangement of neuronal connectivity. To study the effects of sustained inhibitory activity on developing inhibitory (GABAergic) neurons, three-dimensional primary cell cultures of fetal rat telencephalon were used. In relatively immature cultures, muscimol (10 microns), a GABAA receptor agonist, induced a transient increase in apoptotic cell death, as evidenced by a cycloheximide-sensitive increase of free nucleosomes and an increased frequency of DNA double strand breaks (TUNEL labeling). Furthermore, muscimol caused an irreversible reduction of glutamic acid decarboxylase activity, indicating a loss of GABAergic neurons. The muscimol-induced death of GABAergic neurons was attenuated by the GABAA receptor blockers bicuculline (100 microns) and picrotoxin (100 microns), by depolarizing potassium concentrations (30 mM KCl) and by the L-type calcium channel activator BAY K8644 (2 microns). As compared to the cholinergic marker (choline acetyltransferase activity), glutamic acid decarboxylase activity was significantly more affected by various agents known to inhibit neuronal activity, including tetrodotoxin (1 micron), flunarizine (5 microns), MK 801 (50 microns) and propofol (40 microns). The present results suggest that the survival of a subpopulation of immature GABAergic neurons is dependent on sustained neuronal activity and that these neurons may undergo apoptotic cell death in response to GABAA autoreceptor activation.

Animals↗

Some circuit operations in the mammalian brain.

There is an account of the basis neuronal connectivities of the spinal cord with the Sherringtonian principles of divergence and convergence. Neurones act synaptically either as excitatory or as inhibitory, depending on the specific transmitter substances liberated. Inhibitory neurones usually act either in a feedback or a feedforward manner. Voluntary movement is considered in relation to the instructions delivered to the motor cortex in order to produce the discharges down the pyramidal tract that evoke the required movement. There is an account of the three lines of evidence which indicate that in voluntary movements the primary neural event arises in discharges of neurones of the supplementary motor area (SMA). There are three main circuits from the SMA that activate subroutines concerned in the preprogramming of movements: (1) SMA to the basal ganglia, thence to the thalamus with a collateral line through the substantia nigra, thence to the association cortex; (2) SMA to cerebellar hemisphere via the pontine nuclei, thence to the nucleus dentatus, to the thalamus, to the association cortex, and (3) SMA to association cortex both frontal and parietal. According to the SMA hypothesis the liaison brain for intention is located in the SMA, there being reciprocity of informational flow from the mental events of intention to the neuronal events in the SMA.

Animals↗

Excitatory amino acid neurotoxicity in the developing brain.

EAA neurotransmitters participate in a variety of physiologic processes during central nervous system development. EAAs function as neurotransmitters but also regulate development of neuronal cytoarchitecture and neuronal connectivity. EAAs play a major role in several forms of activity-dependent synaptic plasticity including learning and memory, and stabilization and elimination of synaptic connections during development. Similar molecular mechanisms may underlie plastic changes during development and neuronal destruction by overaction of EAA receptors. A critical level of EAA neurotransmitter activity is required for normal development. However, there appears to be a continuum of physiologic reactions to EAA receptor activation: underactivation can retard or disrupt normal development, whereas overactivation can lead to neuronal injury and destruction (figure 8). The susceptibility of the brain to excitotoxicity is dramatically altered during postnatal development. As a result of these changes, the contribution of NMDA receptor activation in excitotoxic brain injury may be greater during early periods of postnatal development, whereas non-NMDA receptors may make a greater contribution to excitotoxic injury in the adult brain.

Animals↗

A method for the identification of pseudorabies virus protein and angiotensin AT(1A) receptor mRNA expression in the same CNS neurons.

Neurotropic viruses have been used over the last 10 years to map the distribution of chains of synaptically connected neurons in the CNS. The peptide content of infected neurons has been determined in a number of cases immunohistochemically. However, it has been unclear whether specific mRNA can be assessed in virus-infected neurons. We have established a technique which enables the identification of viral protein and mRNA in the same neuron. In the present study pseudorabies virus retrogradely transported from the kidney was localised using immunohistochemistry and mRNA for the angiotensin II AT(1A) receptor was detected by hybridisation histochemistry. Virus protein was visualised using an immunohistochemical procedure with diaminobenzidine as the chromogen and the same sections were exposed to radioactively labelled ((35)S) riboprobes, hybridising the angiotensin II AT(1A) receptor. The combination of these two approaches resulted in the identification of neurons shown to project polysynaptically to the kidney and express AT(1A) mRNA. These data provide neuroanatomical support for previous physiological observations that ablation of the lamina terminalis and administration of losartan, the AT(1) receptor antagonist, blocks the inhibition of renal sympathetic nerve activity following centrally injected Ang II in rats and sheep [5].

Animals↗

A Golgi-electron microscopic study of goldfish optic tectum. II. Quantitative aspects of synaptic organization.

The size, density, and number of the synaptic contacts of three types of interneurons (types I, III, and XIV of Meek and Schellart, '78) and three types of efferent neurons (types VI, XII, and XIII) of the goldfish optic tectum were quantified by means of a quantitative stereological study of Golgi-EM serial sections. Furthermore, an estimation was made of the percentage of optic terminals on these six cell types and of the ratio between terminals with pleomorphic and terminals with round vesicles. The mean density of contacts per receptive component (i.e. the cell body and the different parts of the dendritic tree) varies from 0 to 100 per 100/micrometer2 surface, corresponding to 0-8% receptive surface. Each cell type has a characteristic average density as well as a characteristic density distribution along the distinct components. This suggests that the receptive components of the tectal cell types investigated have a predetermined density and that a morphological classification of tectal cells has functional relevance. The mean length of the contact zones in the ultrathin sections varies from 213 to 332 nm for identified postsynaptic elements and from 188 to 293 nm for identified presynaptic elements. The size of the contacts on the distinct receptive components appears to be primarily related to the tectal lamination pattern. Distinct types of axons, however, have characteristic mean sizes of contacts. This might suggest that the size of the contacts, contrary to their density, is primarily determined by the presynaptic elements. The mean number of synaptic contacts calculated per cell type is as follows: type XIV, 200; type III, 450; type VI, 1,400; type I, 2,100; type XII, 4,200; and type XIII, 5,400. Multiplication of these numbers with the number of cells per tectal half shows that the population of type XIV cells has by far the most synaptic contacts, since their low number of synaptic contacts is clearly overruled by their high frequency of occurrence. Optic terminals, identified by their characteristic mitochondria and large round vesicles, appear to contribute to about 10-20% of the contacts on identified post-synaptic elements in layer 5. The ratio between presynaptic elements with pleomorphic vesicles and those with round vesicles shows a slight tendency to increase when the distance to the origin of the axon decreases. It is concluded that a combination of the Golgi-EM technique with quantitative stereological methods appears well suited to the study of the synaptic organization of brain centers, and that combination of quantitative Golgi-EM with neuronal tracing methods (degeneration, HRP, autoradiography) offers good prospects for detailed investigations of neuronal connectivity.

Animals↗

Monoamines and neuropeptides in antennal lobe interneurons of the desert locust, Schistocerca gregana: an immunocytochemical study.

As a first step towards unravelling some of the complexity of the signalling and modulatory mechanisms in the antennal lobe (AL) of the desert locust Schistocerca gregaria, I analysed the immunocytochemical identity of AL interneurons. Antibodies against serotonin, histamine, locustatachykinin, leucokinin and FMRFamide were used to reveal the morphology of interneurons ramifying in the AL. In addition, double-labelling experiments were performed in order to demonstrate colocalisation of GABA and locustatachykinin and to investigate the ramification patterns of immunolabelled interneurons and physiologically characterised olfactory projection neurons (PNs) injected with Lucifer yellow. Immunoreactivity to these antibodies revealed six different types of interneurons with different patterns of ramification within the glomerular neuropil: (1, 2) Centrifugal interneurons displaying serotonin immunoreactivity, which arborised extensively within the AL and extended varicose fibres into the microglomerular core where close associations with dendrites of AL PNs could be distinguished. (3) Histamine-immunoreactive centrifugal interneurons with arborisations in the protocerebrum and the dorsal non-glomerular regions of the AL and the lobus glomerulatus (LG). (4) Locustatachykinin-immunoreactive local interneurons, colocalising GABA, arborising throughout the AL and extending varicose fibres throughout the glomerular neuropil where close associations with dendrites of AL PNs could be distinguished. (5) Leucokinin-immunoreactive descending neurons connecting the protocerebrum, the AL, the LG and all ganglia of the ventral nerve cord. These neurons displayed sparse innervation of the AL and extended varicose fibres into the interglomerular space. (6) FMRF-amide-immunoreactive centrifugal interneurons, connecting the lateral protocerebrum with the AL and the LG, which arborised sparsely within these neuropils and displayed similar innervation of the microglomeruli as (1) and (2).

Animals↗

Synaptic transmission between individual pyramidal neurons of the rat visual cortex in vitro.

Synaptic transmission between pairs of neurons in layer 2/3 of in vitro slices from the rat visual cortex was studied by dual intracellular recording. The intrinsic electrophysiological properties of these neurons suggested that they were pyramidal cells. More than 1/3 of the total number of synaptically connected neurons were stained by intracellular iontophoresis of biocytin, and all had pyramidal morphology. Postsynaptic potentials (PSPs) were evoked by single action potentials (elicited by current injection) in presynaptic cells. Measurements of PSP latency, amplitude, and shape were made on spike-triggered averages. Forty-eight synaptic connections were found out of a possible total of 549, equivalent to a probability of about 0.09. For these 48 connections, the distance between the 2 impalement sites ranged from 50 to 340 microns. All PSPs were depolarizing at rest (-74 +/- 5 mV, mean +/- SD), and all 14 of the PSPs that were also recorded with the postsynaptic cell depolarized to around action potential threshold (about -55 mV) remained depolarizing. PSPs had short latencies (1.2 +/- 0.6 msec, mean +/- SD), suggesting that they were mediated by monosynaptic pathways. Peak amplitudes of the averaged PSPs varied widely (range, 0.05-2.08 mV), but the majority were less than 0.5 mV. PSPs decayed exponentially with time constants that were correlated with, but slightly longer than, the membrane time constants of the postsynaptic cells measured using injected current pulses. Four cell pairs were connected reciprocally, and 6 examples of convergent input were found in which a single cell was postsynaptic to more than 1 presynaptic cell. Trial-to-trial fluctuations in PSP amplitude were analyzed for 16 synaptic connections. The amplitude of the PSP evoked by a presynaptic action potential fluctuated more than could be accounted for by the background noise.

Action Potentials↗