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At least 991 records · Page 55Linked to original sources
PubMed1995

Emergence of a synaptic neuronal network within primary striatal cultures seeded in serum-free medium.

In order to investigate the basic cellular mechanisms involved in neuronal interactions within the striatum, we prepared a primary striatal cell culture from rat fetal brain in chemically defined medium. Using morphological and whole-cell recording methods, we observed that an intensive neuritic elongation with a progressive build up of a sodium-dependent electrogenesis occurred during the first week of culture. Morphologically mature synapses began to develop after 10 days in vitro. By this time, most of the neurons (82 +/- 9%) received spontaneously synaptic potentials, which led them to fire (71 +/- 11%). The spontaneous firing was prevented by cadmium (200 microM) and tetrodotoxin (5 microM), which suggested that a Ca(2+)-dependent release of neurotransmitters was involved in the synaptic activation. We further obtained evidence that GABA, and to a lesser extent acetylcholine, contributed to these spontaneous synaptic potentials. At 15 days in vitro, it was possible to observe up to four synaptic contacts on a given dendrite. By this time, whole-cell recordings performed on pairs of neurons showed that the mature neurons were interconnected by excitatory synapses. As the number of synapses increased, the striatal neurons gradually formed a large network in which spontaneous activity developed, which tended to be organized into synchronized bursting patterns.

Action Potentials↗
PubMed1997

Fear conditioning induces a lasting potentiation of synaptic currents in vitro.

The amygdala plays a critical role in the mediation of emotional responses, particularly fear, in both humans and animals. Fear conditioning, a conditioned learning paradigm, has served as a model for emotional learning in animals, and the neuroanatomical circuitry underlying the auditory fear-conditioning paradigm is well characterized. Synaptic transmission in the medial geniculate nucleus (MGN) to lateral nucleus of the amygdala (LA) pathway, a key segment of the auditory fear conditioning circuit, is mediated largely through N-methyl-D-aspartate (NMDA) and non-NMDA (such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)) glutamate receptors; the potential for neural plasticity in this pathway is suggested by its capacity to support long-term potentiation (LTP). Here we report a long-lasting increase in the synaptic efficacy of the MGN-LA pathway attributable to fear-conditioning itself, rather than an electrically induced model of learning. Fear-conditioned animals show a presynaptic facilitation of AMPA-receptor-mediated transmission, directly measured in vitro with whole-cell recordings in lateral amygdala neurons. These findings represent one of the first in vitro measures of synaptic plasticity resulting from emotional learning by whole animals.

Amygdala↗
PubMed2006

Ethanol potentiates GABAergic synaptic transmission in a postsynaptic neuron/synaptic bouton preparation from basolateral amygdala.

Interactions between ethanol and synaptic transmission mediated by gamma -amino-N-butyric acid (GABA) have been suggested to contribute to alcohol intoxication. Ethanol effects on postsynaptic GABAA receptors have been the major focus of this line of research. There is increasing evidence that ethanol potentiation of GABAergic transmission involves increased GABA release from presynaptic terminals. In the present study, a mechanically isolated neuron/bouton preparation from the basolateral amygdala was used to examine the effects of ethanol on spontaneous GABAergic synaptic currents elicited by GABA release from the presynaptic terminals. We found that ethanol application produced a rapid increase in the frequency of spontaneous GABAergic synaptic currents. An acute tolerance to ethanol was also observed, and this tolerance involved GABAB receptor activation. The ethanol-induced potentiation did not involve alterations in the function of postsynaptic GABAA receptors and was independent of presynaptic action potential firing. These findings indicate that ethanol potentiates GABA release, most likely via a direct action on presynaptic boutons.

Action Potentials↗
PubMed1970

Monosynaptic chemical and electrical connexions between sensory and motor cells in the central nervous system of the leech.

The synaptic connexions that underlie three different segmental shortening reflexes have been traced by recording intracellularly from individual sensory and motor nerve cells in the C.N.S. of the leech. The fourteen sensory cells involved in these reflexes respond specifically to one of three modalities: touch, pressure, or noxious stimuli applied to the skin. All three types of sensory neurone give rise to excitatory synaptic potentials in two large motoneurones. Each of these motor cells provides excitatory innervation to the longitudinal muscle fibres of the opposite side of the segment. The mechanism of synaptic transmission is, however, different for each type of sensory cell.1. An impulse in a sensory cell that responds to touch gives rise to a short-latency depolarizing potential in the large longitudinal motoneurones by way of an electrical synapse. This junction rectifies so that excitation can spread in only one direction (from the sensory to the motor cell), whereas a hyperpolarizing potential can pass only in the opposite direction.2. The synaptic potential evoked in the motoneurone by an action potential in a sensory cell responding to noxious stimuli can be attributed to the action of a chemical transmitter agent and has different properties: the post-synaptic potential arises after a delay of about 2-4 msec, is abolished by high concentrations of Mg, and enhanced by high concentrations of Ca. Several lines of evidence show that this connexion is monosynaptic.3. The synaptic potential following an impulse in a pressure cell is produced by both chemical and electrical synaptic mechanisms. Rectification, similar to that described for the touch cell, also occurs at this electrical synapse.4. One or more impulses in any one of the fourteen mechanoreceptor cells in the ganglion can initiate impulses in the large longitudinal motoneurones to produce a shortening of the segment. The contraction is abolished by blocking impulse initiation in the motoneurones.5. The arborizations of the sensory cells and the motoneurone within the neuropile have been studied histologically after injecting a fluorescent dye. Their processes are intertwined in a highly complex manner so that the sites of the synaptic junctions cannot be determined with the resolutions so far achieved. Nevertheless, taken together the histological and the electrical results support the idea that individual cells are connected in a stereotyped pattern and operate by distinctive mechanisms.6. These findings provide a basis for studying the functional role of chemical and electrical synaptic mechanisms in these pathways.

Action Potentials↗
PubMed1984

Synaptic mechanisms of directional selectivity in ganglion cells of frog retina as revealed by intracellular recordings.

In order to analyze mechanisms of directional selectivity in retinal ganglion cells, synaptic potentials were recorded intracellularly in the eye-cup preparation of the bullfrog. Some preparations were perfused with tetrodotoxin to isolate the synaptic potentials from spike discharges. The cells were classified into ON-OFF-, ON-, and OFF-type by the responses to a stationary flashing light. About 40% of the cells in each type showed directional selectivity to a moving stimulus across their receptive fields. ON-OFF-type cells produced both EPSP and IPSP, and their amplitudes varied depending on the direction of stimulus movement. These findings suggest that the directional selectivity in ON-OFF-type cells could be attributed to the balance of counter-acting postsynaptic potentials. On the other hand, ON- and OFF-type cells responded to the moving stimuli only with EPSP's, and no IPSP was detected. An EPSP evoked by the preferred movement of stimulus was larger in amplitude than that produced by the null movement, thus resulting in directional selectivity. The neural mechanism responsible for the difference in EPSP amplitude in ON- and OFF-type cells probably lies presynaptic to the ganglion cells.

Animals↗
PubMed1990

Properties of single neurons in the cat midsuprasylvian gyrus.

Responses of cells in the midsuprasylvian gyrus (MSSG) of cats were investigated following electrical stimulation of the central lateral nucleus (CL) of the thalamus and tooth pulp, low-threshold cutaneous or visual afferents. Electrical stimulation in CL induced excitation in many cells located in cortical areas 5 and 7. Cells in these areas also received input from somato-sensory and visual afferents. Cells in MSSG showed a wide convergence from tooth pulp, low-threshold cutaneous afferents and from the CL. The majority of wide convergent cells in area 5 were found in layers IV and V, while cells excited by CL and tooth pulp were found in layers II and III. Similarities were found between CL and tooth pulp evoked responses with regard to the excitation-inhibition pattern. The excitation evoked from CL and tooth pulp was less often followed by a hyperpolarizing potential compared to that seen after low-threshold lip, paw and visual afferent stimulation. Stimulation sites in the lateral parts of CL-evoked responses with the shortest latencies in area 5. In this part of the cortex, short latency synaptic potentials were found in cells in superficial layers. In the same area, synaptic potentials of short latency were also evoked by electrical stimulation of tooth pulp, lip and paw. Light-flash stimulation evoked responses with the shortest latencies in area 7. The results of this study demonstrate that putative nociceptive information reaches the parietal association cortex and that part of this input may be relayed via CL. We suggest that the excitatory influences of nociceptive and CL stimulation is related to behavioral arousal and attention mechanisms.

Afferent Pathways↗
PubMed1988

The involvement of nonspiking cells in long-term potentiation of synaptic transmission in the hippocampus.

In guinea pig hippocampal slices, stimulation of stratum radiatum during depolarization (with intracellular current injections) of nonspiking cells (presumed to be glia) in the apical dendritic area of CA1 pyramidal neurons resulted in a subsequent long-term potential of intracellularly recorded excitatory postsynaptic potentials as well as extracellularly recorded population spikes in the CA1 area. Tetanic stimulation of stratum radiatum resulted in a subsequent prolonged depolarization of the presumed glial cells, and this depolarization was smaller when the tetanus was given during the presence of 2-amino-5-phosphonovalerate or when the slices were exposed to Ca2+-free medium containing Mn2+ and Mg2+. These results suggest that glial depolarization is involved as one of the steps in generating long-term potentiation.

Action Potentials↗
PubMed2004

Vestibulo-reticular projections in adult lamprey: their role in locomotion.

This study describes the anatomical projections from vestibular secondary neurons to reticulospinal neurons in the adult lamprey and the modulation of vestibular inputs during fictive locomotion. Anatomical tracers were applied in the posterior (PRRN) and middle rhombencephalic reticular nuclei as well as to the proximal stumps of cut vestibular nerve branches to identify the neurons projecting to the reticular nuclei that were in close proximity with vestibular primary afferents. Labeled neurons were found in the intermediate (ION) and posterior (PON) octavomotor nuclei, and were more numerous on the side of the injection (around 56-87 and 101-107 for the ION and the PON, respectively). Morphologies varied but cells were mostly round or oval. Axonal projections from the PON formed a dense bundle, whereas those from the ION were less densely packed. Based on their morphology and the distribution of their projections, most vestibulo-reticular neurons were presumed to be vestibulospinal cells. Reticulospinal cells from the PRRN were recorded intracellularly in the in vitro brainstem-spinal cord preparation and large excitatory post-synaptic potentials (EPSPs) were evoked following stimulation of the ipsilateral anterior and the contralateral posterior branches of the vestibular nerves, whereas inhibitory post-synaptic potentials (IPSPs) or smaller EPSPs were elicited by stimulation of the ipsilateral posterior or of the contralateral anterior branches. During fictive locomotion, both the excitatory and the inhibitory responses displayed phasic changes in amplitude such that the amplitude of the EPSPs was minimal when the spinal cord activity switched from the ipsilateral to the contralateral side of the recorded reticulospinal cell. The IPSPs were then of maximal amplitude. We propose that this modulation could serve to reduce the influence of vestibular inputs in response to head movements during locomotion.

Animals↗
PubMed1997

5-HT inhibits lateral entorhinal cortical neurons of the rat in vitro by activation of potassium channel-coupled 5-HT1A receptors.

Serotonin (1-40 microM) reduced input resistance by 20.6 +/- 6% and hyperpolarized stellate and pyramidal neurons of layers two and three of the lateral entorhinal cortex. 5-Carboxamidotryptamine, a 5-HT1 agonist, and the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin mimicked the action of serotonin. The reversal potential of 5-HT-mediated hyperpolarizations was sensitive to the extracellular K+ concentration, indicating a potassium conductance change. Serotonin treatment suppressed excitatory amino acid-mediated synaptic potentials (by 48%, Kd = 6.9 microM) and responses to exogenously applied glutamate (70.1 +/- 17% of control, n = 7), but did not alter paired-pulse facilitation, indicating a postsynaptic site of action. Intracellular application of QX-314, a blocker of potassium conductance, significantly reduced depression of synaptic potentials by 5-HT agonists. In cells filled with QX-314, responses to exogenously applied glutamate were not reduced by serotonin or 5-carboxamidotryptamine application. These results indicate that the observed conductance increase associated with 5-HT application accounts for most if not all of the observed depressant effects of 5-HT1A agonists on excitatory amino acid-mediated neurotransmission.

2-Amino-5-phosphonovalerate↗
PubMed1995

Indirect potentiation of synaptic transmission by metabotropic glutamate receptors in the rat hippocampal slice.

The role that the metabotropic glutamate receptor plays in synaptic transmission is complex due to the multiple subtypes involved, which initiate a number of intracellular mechanisms. Here we have investigated the role of the metabotropic glutamate receptor in the induction of long-term potentiation (LTP). We have shown that, providing the CA3 region remains attached to the slice, it is possible to induce potentiation by bath perfusion of the metabotropic receptor agonist (1S,3R) 1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) alone. The extent of the potentiation observed showed a strong negative correlation with the age of the animal from which the slices were prepared. Perfusion of ACPD was associated with an increase in the excitability of antidromically activated CA3 neurones, the appearance of spontaneous burst firing within the CA3 region, and an increased fibre volley recorded in the CA1 region. Blockade of N-methyl-D-aspartate (NMDA) receptors prevented all these effects. We suggest that the ACPD-induced potentiation of CA1 fEPSPs is an indirect effect caused by spontaneous burst firing and/or increased excitatory drive from CA3 neurones.

2-Amino-5-phosphonovalerate↗
PubMed1991

Local information processing in dendritic trees: subsets of spines in granule cells of the mammalian olfactory bulb.

The anaxonic granule cell of the olfactory bulb is believed to inhibit mitral and tufted cells through reciprocal dendrodendritic synapses. However, little is known about the detailed input-output properties of the granule cell. This study explores the functional properties of granule cells by using detailed reconstructions of Golgi-impregnated granule cells as the basis for computational models. Three Golgi-impregnated granule cells from the olfactory bulbs of C57BL/6j mice were selected for detailed analysis. Measurements were made of the diameter and length of all spine heads, spine necks, and dendritic branches. These measurements formed the basis of a compartmental model of each cell in which simulations of the spread of synaptic potentials within the dendritic tree were performed with SABER (Analogy, Inc.), a circuit analysis program. The results show that the degree of spread of synaptic potentials can define functionally related subsets of spines within the dendritic tree. The size of these subsets varies with the anatomical location of the input spine, the magnitude of the input, the time course of the input, the size of the spine neck resistance, and the activity of other spines. The data indicate that the functional organization of granule cell dendritic arbors is more complex than previously thought: between the level of the individual spine and the entire dendritic tree are several levels of subsets of spines that can mediate discrete localized inhibition onto subsets of mitral or tufted cell secondary dendrites within the external plexiform layer of the olfactory bulb.

Animals↗
PubMed2004

The type IV-specific phosphodiesterase inhibitor rolipram and its effect on hippocampal long-term potentiation and synaptic tagging.

We investigated the effects of rolipram, a selective cAMP phosphodiesterase (PDE) inhibitor, on late plastic events during functional CA1 plasticity in vitro in rat hippocampal slices. We present data showing that an early form of long-term potentiation (LTP) (early-LTP) that normally decays within 2-3 hr can be converted to a lasting LTP (late-LTP) if rolipram is applied during tetanization. This rolipram-reinforced LTP (RLTP) was NMDA receptor and protein synthesis dependent. cAMP formation in region CA1 during late-LTP requires dopaminergic receptor activity (Frey et al., 1989, 1990). Thus, we studied whether RLTP was influenced by inhibitors of the D(1)/D(5) receptor. Application of the specific D(1)/D(5) antagonist SCH23390 (0.1 microm) did not prevent RLTP, suggesting that the phosphodiesterase inhibitor acts downstream of the D(1)/D(5) receptors. We also studied whether rolipram can interact with processes of synaptic tagging, because RLTP was also dependent on protein synthesis, similar to late-LTP. Inhibition of PDE and subsequent induction of RLTP in one synaptic population were able to transform early-LTP into late-LTP in a second, independent synaptic population of the same neurons. This supports our hypothesis that cAMP-dependent processes are directly involved in the synthesis of plasticity-related proteins.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

Receptive fields of cricket giant interneurones are related to their dendritic structure.

The structural relationship between the afferent projection and the dendrites of the interneurones was examined in the cercal-to-giant interneurone system of the cricket using intracellular recording and dye injection techniques. The physiology of the sensory neurones beneath the cercal filiform hairs was investigated by placing a recording pipette over the end of a cut hair and using movements of the pipette to characterize the directionality of the receptor. Most of the filiform receptors could be classified as belonging to one of four major types. Each type is sensitive to a different wind direction and is confined to particular regions of the cercus. The location of the terminal arborizations of each type of sensory cell was revealed by staining with cobalt chloride. Single cells were stained reliably by placing a dye-filled pipette over a cut hair. Each physiological receptor type arborizes in a different region of the central nervous system. Therefore the neuropile is functionally divided according to wind direction. The dendrites of three identified interneurones were examined in the context of this afferent projection. It was found that each of these neurones has dendrites in regions of neuropile corresponding to different wind directions. By searching for unitary synaptic potentials in identified interneurones, it was possible to show a strong correlation between anatomical overlap of primary afferent and interneurone and the existence of a synaptic connexion. Further, when there was no overlap, no synaptic potentials were seen. Therefore the over-all excitatory receptive field of an interneurone could be predicted by examining its dendritic structure. Each of the three identified interneurones examined in this study was found to have a directional response that matched the response predicted on the basis of its anatomy.

Action Potentials↗
PubMed2002

Metabotropic glutamate 2 receptors modulate synaptic inputs and calcium signals in striatal cholinergic interneurons.

Striatal cholinergic interneurons were recorded from a rat slice preparation. Synaptic potentials evoked by intrastriatal stimulation revealed three distinct components: a glutamatergic EPSP, a GABA(A)-mediated depolarizing potential, and an acetylcholine (ACh)-mediated IPSP. The responses to group II metabotropic glutamate (mGlu) receptor activation were investigated on the isolated components of the synaptic potentials. Each pharmacologically isolated component was reversibly reduced by bath-applied LY379268 and ((2S,1'R,2'R,3'R)-2-(2,3-dicarboxylcyclopropyl)-glycine, group II agonists. In an attempt to define the relevance of group II mGlu receptor activation on cholinergic transmission, we focused on the inhibitory effect on the IPSP, which was mimicked and occluded by omega-agatoxin IVA (omega-Aga-IVA), suggesting a modulation on P-type high-voltage-activated calcium channels. Spontaneous calcium-dependent plateau-potentials (PPs) were recorded with cesium-filled electrodes plus tetraethylammonium and TTX in the perfusing solution, and measurements of intracellular calcium [Ca2+]i changes were obtained simultaneously. PPs and the concomitant [Ca2+]i elevations were significantly reduced in amplitude and duration by LY379268. The mGlu-mediated inhibitory effect on PPs was mimicked by omega-Aga-IVA, suggesting an involvement of P-type channels. Moreover, electrically induced ACh release from striatal slices was reduced by mGlu2 receptor agonists and occluded by omega-Aga-IVA in a dose-dependent manner. Finally, double-labeling experiments combining mGlu2 receptor in situ hybridization and choline acetyltransferase immunocytochemistry revealed a strong mGlu2 receptor labeling on cholinergic interneurons, whereas single-label isotopic in situ hybridization for mGlu3 receptors did not show any labeling in these large striatal interneurons. These results suggest that the mGlu2 receptor-mediated modulatory action on cell excitability would tune striatal ACh release, representing an interesting target for pharmacological intervention in basal ganglia disorders.

Acetylcholine↗
PubMed1978

A depolarizing inhibitory potential in neurones of the olfactory cortex in vitro.

1. Stable intracellular recordings were obtained from neurones in slices of the guinea-pig olfactory cortex maintained in vitro. 2. Single stimuli applied to the lateral olfactory tract (l.o.t.) produced an excitatory post-synaptic potential (e.p.s.p.) usually generating a single spike. 3. The e.p.s.p. was followed by a long (200-500 msec) after-depolarization (l.a.d.) of peak amplitude 5-16 mV. This was accompanied by a very large conductance increase and was associated with an inhibition of the intracellularly recorded e.p.s.p. and of spike generation. 4. The l.a.d. was more susceptible than the e.p.s.p. to depression by (i) repetitive l.o.t. stimulation and (ii) raising external [Mg2+]. The l.a.d. could be generated without a preceding spike. 5. At an average resting membrane potential of -74 mV the average reversal potential for the l.a.d. (El.a.d.) was -63 mV.El.a.d. became more positive on reducing [Cl-]out or on using KCl-filled electrodes. 6. It is concluded that the l.a.d. represents a Cl- -mediated inhibitory post-synaptic potential, generated through deep-lying recurrent inhibitory loops.

Action Potentials↗