Biomedical subjects

V B Aramakis

Publications and source records attributed to V B Aramakis.

8 recordsLinked to original sources

PubMed2001

Metabotropic glutamate receptors modify ionotropic glutamate responses in neocortical pyramidal cells and interneurons.

In neocortex glutamate activates ionotropic and metabotropic receptors (mGluRs). Whole-cell current-clamp recordings in the in vitro rat auditory cortex at 32 degrees C were used to explore the role that mGluRs have in regulation of AMPA/kainate, NMDA, and GABA receptor-mediated synaptic transmission. Our findings are: (a) The fast EPSP (AMPA/kainate), slow EPSP (NMDA), and IPSPs (GABAA, GABAB), elicited in pyramidal neurons are reduced in the presence of (1S,3R)-ACPD (mGluR agonist) with greatest effect on the slow IPSP>fast IPSP>>fast EPSP. The effect is likely the result of ACPD acting at presynaptic mGluRs because the probability of release of glutamate and GABA is reduced in the presence of ACPD, intracellular infusion of a G protein antagonist (GDPPS) did not block the effect of ACPD, nor were iontophoretic kainic acid or NMDA-induced depolarizations reduced by ACPD. (b) The slow EPSP is enhanced following washout of ACPD and enhancement is not due to disinhibition because it is present in the absence of IPSPs, but if IPSPs are present, its magnitude can be influenced. Iontophoretic NMDA responses are enhanced in the presence of ACPD, an effect blocked by GDPbetaS and heparin (intracellular inositol 1,4,5-trisphosphate receptor antagonist). Taken together, this evidence suggests that enhancement is a result of group I postsynaptic mGluR activation. (c) In fast-spiking cells ACPD reduces the EPSP (AMPA/kainate and NMDA-mediated). This action is likely presynaptic because it persists when GDPbetaS is in the cells. (d) The rate of spike discharge recorded from fast-spiking cells is accelerated in ACPD but does not change in the presence of GDPbetaS, suggesting a postsynaptic effect. Our data indicate that mGluRs can influence neocortical synaptic transmission in complex ways by acting presynaptically and postsynaptically.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2000

A critical period for nicotine-induced disruption of synaptic development in rat auditory cortex.

Cholinergic markers in the middle layers of rat auditory cortex are transiently upregulated during the second postnatal week, at which time alpha 7 nicotinic acetylcholine receptors (nAChRs) selectively regulate NMDA receptor (NMDAR)-mediated EPSPs. To investigate the developmental role of this regulation, we determined whether manipulating nAChR function at specific times during the first 4 weeks after birth could alter subsequent neuronal function. Rat pups were injected twice daily with nicotine (1 or 2 mg/kg) or saline during approximately the first, second, or fourth postnatal week (i. e., before, during, or after the peak upregulation of nAChRs). Glutamate EPSPs and intrinsic membrane properties were measured during whole-cell recordings from visually identified pyramidal neurons in layers II-IV of brain slices prepared at least 15 hr after the last injection. Chronic nicotine exposure (CNE) had little effect on intrinsic membrane properties and during week 1 or 4 did not affect synaptic function. However, CNE during week 2 resulted in EPSPs with long durations, multiple peaks, and enhanced NMDAR components. These changes remained significant even 10 d after CNE. Rapid application of nicotine, which in control neurons selectively enhances NMDAR EPSPs during week 2, produced only weak effects after CNE. Receptor binding studies showed that CNE-induced EPSP alterations occurred in the absence of altered alpha 7 nAChR numbers or agonist binding affinity. Thus, altered stimulation of nAChRs by CNE during week 2, but not before or after, disrupts the development of glutamate synapses in rat auditory cortex.

Age Factors↗

PubMed1999

Role of muscarinic receptors, G-proteins, and intracellular messengers in muscarinic modulation of NMDA receptor-mediated synaptic transmission.

Previously, we reported that activation of muscarinic receptors modulates N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission in auditory neocortex [Aramakis et al. (1997a) Exp Brain Res 113:484-496]. Here, we describe the muscarinic subtypes responsible for these modulatory effects, and a role for G-proteins and intracellular messengers. The muscarinic agonist oxotremorine-M (oxo-M), at 25-100 microM, produced a long-lasting enhancement of NMDA-induced membrane depolarizations. We examined the postsynaptic G-protein dependence of the modulatory effects of oxo-M with the use of the G-protein activator GTP gamma S and the nonhydrolyzable GDP analog GDP beta S. Intracellular infusion of GTP gamma S mimicked the facilitating actions of oxo-M. After obtaining the whole-cell recording configuration, there was a gradual, time-dependent increase of the NMDA receptor-mediated slow-EPSP, and of iontophoretic NMDA-induced membrane depolarizations. In contrast, intracellular infusion of either GDP beta S or the IP3 receptor antagonist heparin prevented oxo-M mediated enhancement of NMDA depolarizations. The muscarinic receptor involved in enhancement of NMDA iontophoretic responses is likely the M1 receptor, because the increase was prevented by pirenzepine, but not the M2 antagonists methoctramine or AF-DX 116. Oxo-M also reduced the amplitude of the pharmacologically isolated slow-EPSP, and this effect was blocked by M2 antagonists. Thus, muscarinic-mediated enhancement of NMDA responses involves activation of M1 receptors, leading to the engagement of a postsynaptic G-protein and subsequent IP3 receptor activity.

Animals↗

PubMed1999

Intrinsic electrophysiology of neurons in thalamorecipient layers of developing rat auditory cortex.

During early postnatal life, several critical events contribute to the functional development of rat sensory neocortex. Thalamocortical innervation of sensory cortex is completed during the first postnatal week and extrathalamic innervation develops over the first several weeks. In auditory cortex, acoustic-evoked potentials first occur in week 2 and develop most rapidly over weeks 2-3. Thus, rapid functional maturation of cortical circuits in sensory cortex occurs during the second and third postnatal weeks. The electrophysiological properties of cortical neurons that receive afferent inputs during this time may play an important role in development and function. In this study we examined the intrinsic electrophysiology, including spiking patterns, of neurons in layers II/III and IV of auditory cortex during postnatal weeks 2 and 3. Many neurons displayed characteristics consistent with previous descriptions of response classes (regular spiking, fast spiking, intrinsic bursting). In addition, we identified two groups, Rectifying and On-spiking neurons, that were characterized by (i) brief spike trains in response to maintained intracellular depolarizations, and (ii) striking outward rectification upon depolarization. Unusually brief spike trains (1-2 spikes) and short spike latencies (<10 ms) further distinguished On-spiking from Rectifying cells. Biocytin labeling demonstrated that On-spiking and Rectifying cells could be either pyramidal or nonpyramidal neurons. The intrinsic physiology of these cell groups may play an important role in auditory cortex function.

Analysis of Variance↗

PubMed1998

Nicotine selectively enhances NMDA receptor-mediated synaptic transmission during postnatal development in sensory neocortex.

The neurotransmitters acetylcholine (ACh) and glutamate have been separately implicated in synaptic plasticity during development of sensory neocortex. Here we show that these neurotransmitters can, in fact, act synergistically via their actions at nicotinic ACh receptors (nAChRs) and NMDA receptors, respectively. To determine how activation of nAChRs modifies glutamatergic EPSPs, we made whole-cell recordings from visualized pyramidal neurons in slices of rat auditory cortex. Pulsed (pressure) ejection of nicotine onto apical dendrites selectively enhanced EPSPs mediated by NMDA receptors without affecting AMPA/kainate (AMPA/KA) receptor-mediated EPSPs. The enhancement occurred during a transient, postnatal period of heightened cholinergic function [neurons tested on postnatal day 8-16 (P8-16)], and not in the mature cortex (>P19). Three related findings indicated the mechanism of action: (1) The specific alpha7 nAChR antagonist methyllycaconitine citrate (MLA) blocked the effect of nicotine; (2) pulsed nicotine did not enhance postsynaptic depolarizations induced by iontophoretically applied NMDA; and (3) bath exposure to nicotine for several minutes produced apparent nAChR desensitization and precluded enhancement of EPSPs by pulsed nicotine. Together, the data suggest that nicotine acts at rapidly desensitizing, presynaptic alpha7 nAChRs to increase glutamate release onto postsynaptic NMDA receptors. The synergistic actions mediated by alpha7 nAChRs and NMDA receptors may contribute to experience-dependent synaptic plasticity in sensory neocortex during early postnatal life.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1997

Muscarinic reduction of GABAergic synaptic potentials results in disinhibition of the AMPA/kainate-mediated EPSP in auditory cortex.

The present study is concerned with the ability of muscarinic actions of acetylcholine (ACh) to modulate glutamate and gamma-aminobutyric acid (GABA)-mediated synaptic transmission in the in vitro rat auditory cortex. Whole-cell patch clamp recordings were obtained from layer II-III pyramidal neurons, and the fast-EPSP (AMPA/kainate), fast-IPSP (GABA(A)), and slow-IPSP (GABA(B)), were elicited following a stimulus to deep gray/white matter. Acetyl-beta-methylcholine (MCh), a muscarinic receptor agonist, applied by either superfusion or iontophoresis, produced an atropine-sensitive increase or decrease in the amplitude of the fast-EPSP. The effect of MCh could be predicted by the response of the fast-EPSP to paired-pulse stimulation (i.e. a conditioning pulse followed 300 ms later by a test pulse). The fast-EPSP was decreased in amplitude by MCh in cases where the test-EPSP was suppressed in the pre-MCh condition, and increased in amplitude when the test-EPSP was facilitated. The fast- and slow-IPSPs were always reduced by MCh. In several experiments, the strength of synaptic inhibition was systematically modified by varying stimulus intensity. When the fast-EPSP was elicited in the absence of IPSPs, it was decreased in amplitude by MCh. However, when the fast-EPSP was elicited in conjunction with large IPSPs it was increased in amplitude during MCh. Because the magnitude of the fast-EPSP is influenced by the degree of temporal overlap with IPSPs, it was hypothesized that enhancement of the fast-EPSP was the result of disinhibition produced as a consequence of muscarinic reduction of GABAergic IPSPs. This view was supported by the finding that MCh could reduce the amplitude of pharmacologically isolated GABAergic IPSPs (i.e. elicited in the absence of glutamatergic transmission). Our results suggest that ACh at muscarinic receptors can modify fast glutamatergic neurotransmission differently as a function of strength of inhibition, to suppress that produced by 'weak' inputs and enhance that produced by 'strong' inputs.

Acetylcholine↗

PubMed1997

Activation of muscarinic receptors modulates NMDA receptor-mediated responses in auditory cortex.

The present study examines the ability of muscarinic receptor activation to modulate glutamatergic responses in the in vitro rat auditory cortex. Whole-cell patch-clamp recordings were obtained from layer II-III pyramidal neurons and responses elicited by either stimulation of deep gray matter or iontophoretic application of glutamate receptor agonists. Iontophoresis of the muscarinic agonist acetyl-beta-methylcholine (MCh) produced an atropine-sensitive reduction in the amplitude of glutamate-induced membrane depolarizations that was followed by a long-lasting (at least 20 min) response enhancement. Glutamate depolarizations were enhanced by MCh when elicited in the presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or 2,3-dihydroxy-6-nitro-7-sulfamoyl, benzo(F)quinoxaline (NBQX) but not the NMDA antagonists D-2-amino-5-phosphonovaleric acid (APV) or MK-801 hydrogen maleate. The magnitude of enhancement was voltage-dependent with the percentage increase greater at more depolarized membrane potentials. An involvement of NMDA receptors in these MCh-mediated effects was tested by using AMPA/kainate receptor antagonists to isolate the NMDA-mediated slow excitatory postsynaptic potential (EPSP) from other synaptic potentials. The slow EPSP and iontophoretic responses to NMDA were similarly modified by MCh, i.e., both being reduced during and enhanced (15-55 min) following MCh application. Cholinergic modulation of NMDA responses involves the engagement of G proteins, as enhancement was prevented by intracellular infusion with the nonhydrolyzable GDP analog guanosine-5'-O-(2-thiodiphosphate) trilithium salt (GDPbetaS). GDPbetaS was without effect on the early MCh-induced response suppression. Our results suggest that acetylcholine, acting at muscarinic receptors, produces a long-lasting enhancement of NMDA-mediated neurotransmission in auditory cortex, and that this modulatory effect is dependent upon a G protein-mediated event.

Acetylcholine↗

PubMed1996

Neuropeptide Y receptor agonists: multiple effects on spontaneous activity in the paraventricular hypothalamus.

In vitro rat hypothalamic slices were used to examine the ability of neuropeptide Y (NPY), and the putative Y1 and Y2 receptor agonists [Pro34]NPY and [C2]NPY, to modify spontaneous single-neuron discharge in the paraventricular nucleus (PVN). NPY and [Pro34]NPY, at high concentrations (1500 nM), decreased discharge rates. At intermediate concentrations (150 nM) these peptides produced multiple effects, including increases, decreases, and biphasic changes. At lower concentrations (0.15-15 nM), they typically increased discharge rates. In contrast, [C2]NPY, at all concentrations (1.5-1500 nM), predominantly increased discharge rates. Thus, these NPY subtype agonists have multiple effects on discharge rate, which may be due to actions on multiple NPY receptor subtypes.

Animals↗