Journal of Neuroscience
0270-6474
1529-2401
Mỹ
Cơ quản chủ quản: Society for Neuroscience , SOC NEUROSCIENCE
Lĩnh vực:
Neuroscience (miscellaneous)
Phân tích ảnh hưởng
Thông tin về tạp chí
To advance neuroscience research by publishing and widely disseminating the highly rigorous research representative of the breadth of neuroscience; to ensure the peer review system remains rapid and fair; and to provide outlets for discussion of neuroscience that are not available elsewhere, allowing for competing ideas, debate, and questions around neuroscience. JNeurosci is a multidisciplinary journal that publishes papers on a broad range of topics of general interest to those working on the nervous system.
Các bài báo tiêu biểu
Differential Regulation of the Mesoaccumbens Circuit by Serotonin 5-Hydroxytryptamine (5-HT)<sub>2A</sub>and 5-HT<sub>2C</sub>Receptors
Tập 21 Số 19 - Trang 7781-7787 - 2001
The Functional Neuroanatomy of Temporal Discrimination Two identical stimuli, such as a pair of electrical shocks to the skin, are readily perceived as two separate events in time provided the interval between them is sufficiently long. However, as they are presented progressively closer together, there comes a point when the two separate stimuli are perceived as a single stimulus. Damage to posterior parietal cortex, peri-supplementary motor area (peri-SMA), and basal ganglia can disturb this form of temporal discrimination. Our aim was to establish, in healthy subjects, the brain areas that are involved in this process. During functional magnetic resonance imaging scanning, paired electrical pulses, separated by variable inter-stimulus intervals (5-110 msec), were delivered to different sites on one forearm (8-64 mm from the midline). Subjects were required to simply detect the stimulus (control task) or to identify a stimulus property. For temporal discrimination (TD), subjects reported whether they felt one or two stimuli. For spatial discrimination, they reported whether the stimuli were located on the right or left side of the forearm. Subjects reported their choice by pressing a button with the opposite hand. Our results showed that discrimination, as opposed to simply detection, activated several brain areas. Most were common to both discrimination tasks. These included regions of prefrontal cortex, right postcentral gyrus and inferior parietal lobule, basal ganglia, and cerebellum. However, activation of pre-SMA and anterior cingulate was found to be specific to the TD task. This suggests that these two frontal regions may play a role in the temporal processing of somatosensory events.
Tập 24 Số 10 - Trang 2585-2591 - 2004
Cocaine inhibits GABA release in the VTA through endogenous 5-HT The ventral tegmental area (VTA) is thought to be involved in the addictive properties of many drugs, including cocaine. It has been hypothesized that cocaine exerts its actions in the VTA by blocking the reuptake of dopamine released from the dendrites of the A10 dopamine neurons, thus prolonging the actions of dopamine at D2 autoreceptors. However, cocaine also blocks the reuptake of the other monoamines, including serotonin (5-HT). Using intracellular recordings from midbrain dopamine neurons in a brain slice preparation, we have found that cocaine (0.1–10 microM) inhibited the GABAB IPSP in a dose- dependent manner. This effect was observed in the presence of the D2 dopamine receptor antagonists sulpiride (1 microM) and eticlopride (0.1 microM). 5-HT mimicked this effect, as did the selective 5-HT1D receptor agonist sumatriptan and the 5-HT-releasing agent fenfluramine. The actions of both 5-HT and cocaine were attenuated by the 5-HT1C/D antagonist metergoline. Pretreatment of slices with the 5-HT-depleting agent p-chloroamphetamine (pCA; 10 microM) abolished the inhibition of the GABAB IPSP by cocaine but failed to affect the actions of sumatriptan. We conclude that cocaine acts to modulate the GABA input to A10 dopamine neurons via inhibition of the 5-HT transporter, increasing the concentration of 5-HT at presynaptic 5-HT1D receptors. These actions of cocaine were apparent at lower concentrations than those required to act via inhibition of the dopamine transporter. This reduction of inhibitory synaptic input into the VTA would be expected to attenuate the GABA-mediated feedback inhibition from the nucleus accumbens, thus leading to increased activation of dopamine neurons.
Tập 14 Số 11 - Trang 6763-6767 - 1994
Enhanced Vulnerability to Cocaine Self-Administration Is Associated with Elevated Impulse Activity of Midbrain Dopamine Neurons Individual differences in responding to a novel environment predict behavioral and neurochemical responses to psychostimulant drugs. Rats with a high locomotor response to a novel environment (HRs) exhibit enhanced self-administration (SA) behavior, sensitization, and basal or drug-induced dopamine release in the nucleus accumbens compared with rats with a low response to the novel context (LRs). In this study, we determined whether such differences in vulnerability to drug addiction might be related to differences in dopamine (DA) neuron activity. Rats were divided into HRs and LRs according to their response to a novel environment and then tested for acquisition of cocaine SA. HRs rapidly acquired cocaine SA (175 μg/kg per infusion), whereas LRs did not. Differences in cocaine SA were not caused by differences in exploratory behavior or sampling because these behaviors did not differ in HRs and LRs self-administering a saline solution. In a separate experiment, we used extracellular single-unit recordings and found that HRs exhibit higher basal firing rates and bursting activity of DA neurons in the ventral tegmental area and, to a lesser extent, in the substantia nigra pars compacta. The greater activity of midbrain DA cells in HRs was accompanied by reduced sensitivity to the inhibitory effects of a DA D2-class receptor agonist, indicating possible subsensitivity of impulse-regulating DA autoreceptors. These results demonstrate that differences in the basal activity of DA neurons may be critically involved in determining individual vulnerability to drugs of abuse.
Tập 20 Số 23 - Trang 8876-8885 - 2000
Properties and Plasticity of Excitatory Synapses on Dopaminergic and GABAergic Cells in the Ventral Tegmental Area Excitatory inputs to the ventral tegmental area (VTA) influence the activity of both dopaminergic (DA) and GABAergic (GABA) cells, yet little is known about the basic properties of excitatory synapses on these two cell types. Using a midbrain slice preparation and whole-cell recording techniques, we found that excitatory synapses on DA and GABA cells display several differences. Synapses on DA cells exhibit a depression in response to repetitive activation, are minimally affected by the GABAB receptor agonist baclofen, and express NMDA receptor-dependent long-term potentiation (LTP). In contrast, synapses on GABA cells exhibit a facilitation in response to repetitive activation, are depressed significantly by baclofen, and do not express LTP. The relative contribution of NMDA and non-NMDA receptors to the synaptic currents recorded from the two cell types is the same as is the depression of synaptic transmission elicited by the application of adenosine, serotonin, or methionine enkephalin (met-enkephalin). The significant differences in the manner in which excitatory synaptic inputs to DA and GABA cells in the VTA can be modulated have potentially important implications for understanding the behavior of VTA neurons during normal behavior and during pathological states such as addiction.
Tập 19 Số 10 - Trang 3723-3730 - 1999
Amphetamine Blocks Long-Term Synaptic Depression in the Ventral Tegmental Area The mesolimbic dopamine system is essential for reward-seeking behavior, and drugs of abuse are thought to usurp the normal functioning of this pathway. A growing body of evidence suggests that glutamatergic synapses on dopamine neurons in the ventral tegmental area (VTA) are modified during exposure to addictive drugs, producing sensitization, a progressive augmentation in the rewarding properties of psychostimulant drugs with repeated exposure. We have tested the hypothesis that psychostimulant exposure interferes with the synaptic plasticity of glutamatergic inputs to the VTA. We find that excitatory synapses onto VTA dopamine neurons exhibit long-term depression (LTD) in response to low-frequency stimulation and modest depolarization. LTD in the VTA is NMDA receptor-independent but is dependent on intracellular Ca2+ and can be induced by driving Ca2+ into the dopamine neuron. Brief exposure to amphetamine entirely blocks LTD at glutamatergic synapses in the VTA, by releasing endogenous dopamine that acts at D2 dopamine receptors. The block of LTD is selective, because amphetamine has no effect on hippocampal LTD. The LTD we have discovered in the VTA is likely to be an important component of excitatory control of the reward pathway; amphetamine will inhibit LTD, removing this normal brake on the glutamatergic drive to dopamine neurons. This effect of amphetamine represents an important mechanism by which normal function of the brain reward system may be impaired during substance abuse.
Tập 20 Số 15 - Trang 5575-5580 - 2000
Amphetamine Depresses Excitatory Synaptic Transmission via Serotonin Receptors in the Ventral Tegmental Area The ventral tegmental area (VTA) is the origination zone for dopaminergic neurons involved in reward and addictive properties of a variety of abused substances. A major excitatory projection to VTA neurons originates in the medial prefrontal cortex, and several lines of evidence suggest that glutamatergic synapses on VTA neurons are activated and modified during exposure to psychostimulant drugs. Here, we report for the first time that amphetamine depresses excitatory glutamatergic synaptic transmission onto VTA neurons in the midbrain slice preparation. Unexpectedly, this depression is mediated not by activation of dopamine receptors, but instead by activation of serotonin receptors. Our findings suggest that an acute effect of amphetamine exposure is the release of serotonin in the VTA, which in turn modulates excitation of VTA neurons. This process may be an important early component of permanent changes occurring in the reward pathway that contribute to drug addiction.
Tập 19 Số 22 - Trang 9780-9787 - 1999
Dual Effects of d-Amphetamine on Dopamine Neurons Mediated by Dopamine and Nondopamine Receptors By increasing dopamine (DA) release and activating feedback mechanisms, amphetamine and related psychostimulants are known to inhibit DA cell firing. Here, we report thatd -amphetamine also has an excitatory effect on DA cells, which under control conditions, is masked by the inhibitory effect ofd -amphetamine and is revealed when D2-like receptors are blocked. Thus, usingin vivo single-unit recording in rats, we found that the selective D2 antagonist raclopride not only blocked the inhibition induced byd -amphetamine but also enabledd -amphetamine to excite DA cells. The excitation, expressed as an increase in both firing rate and bursting, persisted when both D1- and D2-like receptors were blocked by SCH23390 and eticlopride, suggesting that it is not mediated by DA receptors. The norepinephrine uptake blocker nisoxetine mimicked the effect ofd -amphetamine, especially the increase in bursting, whereas the 5-HT uptake blocker fluoxetine produced no significant effect. Adrenergic α1 antagonists prazosin and WB4101 and the nonselective α antagonist phenoxybenzamine completely blocked increase in bursting induced byd -amphetamine and partially blocked the increase in firing rate. The α2 antagonist idazoxan and the β antagonist propranolole, however, failed to preventd- amphetamine from producing the excitation. Thus, revising the traditional concept, this study suggests thatd- amphetamine has two effects on DA cells, a DA-mediated inhibition and a non-DA-mediated excitation. The latter is mediated in part through adrenergic α1 receptors.
Tập 20 Số 9 - Trang 3504-3511 - 2000
Efflux of dopamine from the synaptic cleft in the nucleus accumbens of the rat brain Synaptic release of dopamine in the nucleus accumbens of the intact rat brain elicited by a single electrical impulse applied to ascending dopaminergic fibers results in extracellular concentrations sufficient to bind the known dopamine receptors. The dopamine concentration observed after four rapid, sequential pulses is exactly four times greater and is unaffected by pharmacological antagonism of dopamine uptake and receptor sites at supramaximal concentrations. Thus, dopamine efflux from the synaptic cleft is not restricted by binding to intrasynaptic proteins on the time scale of the measurements (50–100 msec). The extracellular concentration, as a result of a single stimulus pulse, is 0.25 microM and is rapidly removed by extrasynaptic uptake. This maximal, transient concentration of dopamine is 60 times higher than steady-state concentrations reported previously using dialysis techniques, illustrating that dopamine extracellular concentrations are spatially and temporally heterogenous. In contrast to ACh transmission at the neuromuscular junction, the dopamine synapse in the telencephalon is designed for the effective efflux of dopamine from the synaptic cleft to the extrasynaptic compartment during neurotransmission.
Tập 14 Số 10 - Trang 6084-6093 - 1994
Presynaptic Regulation of Glutamate Release in the Ventral Tegmental Area During Morphine Withdrawal The regulation of glutamate (Glu) release from the excitatory input to dopamine cells in the ventral tegmental area (VTA) during acute withdrawal from morphine was studied in slices from animals treated for 6–7 d with morphine. EPSCs were inhibited by opioid agonists acting at μ-subtype receptors but not by selective δ- or κ-subtype agonists. The opioid inhibition was reduced by 65% with the potassium channel blocker 4-aminopyridine (4-AP; 100 μm ) and a 12-lipoxygenase inhibitor, baicalein (5 μm ), suggesting that opioids acted via a transduction pathway involving activation of a voltage-dependent potassium conductance by lipoxygenase metabolites as has been shown in the periaqueductal gray (Vaughan et al., 1997). During withdrawal, neither the potency nor the efficacy ofd -Ala-Met-enkephalin-Gly-ol (DAMGO) were changed; however, the blockade of μ-opioid inhibition by both 4-AP and baicalein was reduced. In addition, the potency of baclofen to depress EPSCs by GABA-B receptors and the effects of the GABA-uptake inhibitor NO-711 (10 μm ) were increased in withdrawn rats. Finally, group 2 (but not group 4 or 1) metabotropic glutamate receptor-mediated presynaptic inhibition was also enhanced in morphine-withdrawn rats. These results suggest that one of the consequences of withdrawal from chronic morphine is an enhanced presynaptic inhibition of the excitatory inputs to the dopamine cells of the VTA. Inhibition of glutamate release during acute withdrawal would add to the inhibition of dopamine cells that is mediated by an augmented release of GABA (Bonci and Williams, 1997).
Tập 19 Số 15 - Trang 6629-6636 - 1999