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C M Pennartz

Publications and source records attributed to C M Pennartz.

27 records · Page 2Linked to original sources

Contribution of NMDA receptors to postsynaptic potentials and paired-pulse facilitation in identified neurons of the rat nucleus accumbens in vitro.

The principal aim of this study was to characterize the transmitter mechanisms mediating fast postsynaptic potentials in identified neurons of the rat nucleus accumbens. Using the biocytin-avidin labeling technique, impaled neurons were identified as medium spiny neurons. The basic membrane characteristics of these neurons were determined. Local electrical stimulation or stimulation of the corpus callosum elicited a depolarizing postsynaptic potential consisting of an EPSP often followed by an IPSP. The quisqualate/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (4 microM) abolished most of the depolarizing postsynaptic potential. The N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid depressed a small part of the decay phase of the depolarizing postsynaptic potential. Paired-pulse facilitation of postsynaptic potentials was found using interstimulus-intervals between 10 and 150 ms. N-methyl-D-aspartate receptors were found to contribute only slightly to the facilitation of the decay phase of the depolarizing postsynaptic potential, but not to its rising phase. This contribution was particularly clear under conditions of reduced GABAA receptor mediated inhibition. The present study indicates that postsynaptic responses of medium spiny neurons in the nucleus accumbens to local stimulation or stimulation of neocortical afferents are primarily mediated by quisqualate/kainate receptors. The contribution of NMDA receptors is normally limited to a portion of the decay phase of these responses, but is enlarged in the absence of GABAergic inhibition and following paired-pulse stimulation.

2-Amino-5-phosphonovalerate↗

Hippocampal inputs to identified neurons in an in vitro slice preparation of the rat nucleus accumbens: evidence for feed-forward inhibition.

The aim of the present study was to analyze responses of nucleus accumbens neurons to stimulation of the fornix. The recorded neurons were labeled with biocytin and identified as medium spiny neurons. A large majority of cells generated a depolarizing postsynaptic potential in response to stimulation of the fornix. Using intracellular current injection, this depolarizing response was dissociated into an EPSP reversing at -6 +/- 6 mV and an IPSP reversing at -71 +/- 4 mV. Both the EPSP and IPSP were abolished by 6-cyano-7-nitroquinoxaline-2,3-dione. In addition, the IPSP was blocked by bicuculline and picrotoxin. The onset latency of the EPSP was constant in spite of varying stimulus intensities. In contrast, the onset latency of the IPSP increased with decreasing stimulus intensity. Notably, the stimulus threshold for evoking IPSPs was generally lower than for EPSPs. At stimulus intensities well above threshold, the IPSP onset was only slightly delayed with respect to the EPSP onset. These results indicate that the EPSP can be characterized as a monosynaptic and glutamate-mediated synaptic response. The IPSP, however, appears to be mediated by a disynaptic feed-forward pathway involving both glutamate and GABAA receptors. Recurrent and lateral inhibitory interactions have previously been proposed to be predominant organizational principles in the caudate-putamen and nucleus accumbens. This study indicates that feed-forward inhibition is an additional principle governing the activities of striatal neural networks.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Locally evoked potentials in slices of the rat nucleus accumbens: NMDA and non-NMDA receptor mediated components and modulation by GABA.

In a slice preparation of the rat nucleus accumbens (Acb), local electrical stimulation elicited a field potential composed of two negative peaks, followed by a positive wave. The early negative peak was identified as a non-synaptic compound action potential, the late negative peak as a monosynaptic population spike (PS) and the positive wave as a mixture of an excitatory and an inhibitory postsynaptic potential (PSP). Both the PS and the PSP exhibited a marked degree of paired-pulse facilitation. The quisqualate/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 2 microM) and the broadly acting glutamate receptor antagonist kynurenic acid (300 microM) reversibly abolished or reduced both the PS and PSP. In contrast, nicotinic, muscarinic and N-methyl-D-aspartate (NMDA) receptor antagonists had no suppressive action. Washout of Mg2+ from the superfusion medium reversibly enhanced and prolonged the PSP and this effect was blocked by the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5). The gamma-aminobutyric acid antagonist picrotoxin (60 microM) enhanced the PS and induced secondary spikes which were superimposed on a prolonged PSP. Most of this prolongation was abolished by D-AP-5. It is concluded that locally evoked synaptic responses in the Acb are mediated by glutamate or aspartate, and that NMDA receptor mediated activity evoked by low frequency stimulation is substantial in Mg2(+)-free medium or during reduced GABAA receptor activity, but not under normal conditions.

2-Amino-5-phosphonovalerate↗

Simulation of movement detection by direction-selective ganglion cells in the rabbit and squirrel retina.

A veto-gate model of movement detection by direction-selective ganglion cells in the vertebrate retina, first proposed by Barlow and Levick (1965), provides the basis for a model described in this study. The model is a simple network consisting basically of (1) two subunits that have receptive fields with a center-surround organization and an adaptational gain control, (2) a lateral inhibitory pathway, (3) a site of nonlinear interaction, followed by (4) a leaky temporal integrator. The model is tested by comparing its basic properties to those reported in the physiological literature on rabbit and squirrel direction-selective retinal ganglion cells. It is shown that the physiological findings on sensitivity to flashes, moving spots or slits, and phi-movement stimuli, can be mimicked quite well by our model. Similarities between the component processes of the subunits and known retinal processes are pointed out. The simulation studies shed a new light on some of the known properties and suggest several new, more revealing, physiological experiments. Such experiments are necessary to develop a full specification of this type of model and to fix more parameter values than is possible at present. Results of some critical experiments are predicted to enable physiologists to falsify or corroborate the model. The simulation studies also help to distinguish use from abuse of this type of model in explanations of psychophysical findings. For example, neither the most complete Barlow-Levick detector nor any stripped-down versions that retain a temporally extended lateral inhibition (which is essential to mimick the physiological findings), respond well to moving random-pixel arrays.

Animals↗

Paired-pulse facilitation in the nucleus accumbens following stimulation of subicular inputs in the rat.

Anatomical tracing studies indicate that the nucleus accumbens receives inputs from limbic structures, and projects to the ventral pallidum. In order to get more fundamental insight into how information from the limbic areas is relayed via the nucleus accumbens, electrophysiological experiments were carried out in rats under halothane anaesthesia. Inputs originating in the subiculum were activated by electrical stimulation of the fornix fibres, and both field potentials and extracellular unit activity were recorded from the medial and lateral aspects of the nucleus accumbens. Evoked potentials consisted of two positive peaks (P1 at 10 ms and P2 at 25-30 ms). In between a negative-going wave (N1) was present. These initial components were followed by a complex negative wave (N2) with variable duration of 30-100 ms. The P2 and N2 components showed a conspicuous paired-pulse facilitation at stimulus intervals between 80 and at least 200 ms. When responses were recorded at increasing stimulus intensity, the second response emerged at lower threshold than the first response. The mechanisms underlying these phenomena were investigated by analysing the extracellularly recorded unit activity. Primarily, excitatory responses were found. Onset-latencies could be divided roughly into two clusters, one around 10 ms, representing monosynaptic inputs, and a second around 24-26 ms. Inhibitory responses were also found. Stimulation of the ventral pallidum was carried out in order to test whether the cells that could be driven by stimulation of the subicular inputs were projection cells. Latencies of antidromic action potentials ranged from 9 to 13 ms. A minority of the identified projection cells were activated by limbic inputs. The projection cells were found in the core region of the nucleus accumbens. Units that were inhibited by stimulation of the limbic inputs were found in the shell only, whereas excitatory responses were measured in both subdivisions of the nucleus accumbens. For the latter responses a significant enhancement, by a factor of four, was found using double pulse stimulation of the fornix at intervals of 100 ms. The basic electrophysiological properties are compared with those described in the literature, and speculations about the possible mechanisms responsible for the paired-pulse facilitation phenomena are put forward.

Action Potentials↗

Eltoprazine suppresses hyperpolarizing responses to serotonin in rat hippocampus.

In this study we report the effects of eltoprazine, a phenylpiperazine derivative with high affinity for 5-hydroxytryptamine1 (5HT1) binding sites, on membrane properties of hippocampal neurons. Intracellular recordings were made from cornus ammoni-1 pyramidal neurons in rat hippocampal slices. Responses to eltoprazine were compared with 5HT-induced responses. Superfusion with 5HT induced a dose-dependent hyperpolarization of the membrane accompanied by a resistance decrease. Eltoprazine evoked membrane changes that were similar to but much weaker than those induced by 5HT. Both the 5HT- and eltoprazine-evoked membrane hyperpolarizations were largely suppressed in the presence of spiperone. The eltoprazine-induced effects persisted in the presence of tetrodotoxin and tetraethylammonium and also when haloperidol and phentolamine were added to the medium, indicating that the small agonistic effects of eltoprazine are not due to an indirect activation of dopamine or alpha adrenergic receptors. Superfusion with eltoprazine furthermore resulted in a marked reduction of the response to concomitantly applied 5HT. Dose-response curves for 5HT were shifted to the right in the presence of eltoprazine, while the maximal response was diminished. Hyperpolarizations induced by baclofen, which presumably activates the same K+ conductance as 5HT, were not significantly reduced by eltoprazine. Our data, added to the previously demonstrated high affinity of eltoprazine for 5HT1 sites, suggest that in the hippocampal cornus ammoni-1 area eltoprazine acts as a partial 5HT1 agonist with a relatively low intrinsic activity but a considerable potency to suppress hyperpolarizing responses to 5HT.

Aggression↗

Quantitative correlation between tetanus-induced decreases in extracellular calcium and LTP.

Decreases in the extracellular calcium concentration ([Ca2+]o), induced by tetanization of the Schaffer collaterals in rat hippocampal slices, were measured by means of Ca2+-sensitive microelectrodes. The amount of long term potentiation (LTP) of the evoked field potentials, induced by this tetanus, was determined. A positive correlation was found between the amplitude of the tetanus induced decrease in [Ca2+]o and the amount of LTP that was elicited. The N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-phosphonovalerate decreased both the tetanus-induced decreases in [Ca2+]o and the amount of LTP that was induced. We conclude that the amount of Ca2+ that enters the cell during a tetanus is of major importance in the induction process of LTP.

2-Amino-5-phosphonovalerate↗

Differential effects of elevated extracellular calcium concentrations on field potentials in dentate gyrus and CA1 of the rat hippocampal slice preparation.

The effect of a short-lasting elevation of the extracellular Ca2+ concentration (from 2 to 6 mM) on the field potentials in CA1 of the rat hippocampal slice was an increase of both the CA1 population spike (PS) and the excitatory postsynaptic potential (EPSP); this effect persisted after returning to 2 mM Ca2+ Ringer, and thus can be considered as a Ca2+-induced long-term potentiation (LTP). In the dentate gyrus (DG) a quite different effect was encountered; here the PS decreased and the EPSP increased only slightly during the perfusion with 6 mM Ca2+, and no reproducible long-term effect was induced. The results indicate that substantial differences exist in the balance between inhibitory and excitatory processes in the neural networks of the two hippocampal subregions; these differences are enhanced during perfusion with high Ca2+, which induces LTP in CA1 but not in the DG.

Animals↗