scholarly journals Distinct prestimulus and poststimulus activation of VTA neurons correlates with stimulus detection

2013 ◽  
Vol 110 (1) ◽  
pp. 75-85 ◽  
Author(s):  
Nelson K. B. Totah ◽  
Yunbok Kim ◽  
Bita Moghaddam
Keyword(s):  
Firing Rate ◽  
Reaction Time Task ◽  
Dopamine Neurons ◽  
Neuron Activity ◽  
Phasic Response ◽  
Preparatory Attention ◽  
Stimulus Detection ◽  
Internal States ◽  
Incorrect Stimulus ◽  
Reward Expectancy

Dopamine neurons of the ventral tegmental area (VTA) signal the occurrence of a reward-predicting conditioned stimulus (CS) with a subsecond duration increase in post-CS firing rate. Important theories about reward-prediction error and reward expectancy have been informed by the substantial number of studies that have examined post-CS phasic VTA neuron activity. On the other hand, the role of VTA neurons in anticipation of a reward-predicting CS and analysis of prestimulus spike rate rarely has been studied. We recorded from the VTA in rats during the 3-choice reaction time task, which has a fixed-duration prestimulus period and a difficult-to-detect stimulus. Use of a stimulus that was difficult to detect led to behavioral errors, which allowed us to compare VTA activity between trials with correct and incorrect stimulus-guided choices. We found a sustained increase in firing rate of both putative dopamine and GABA neurons during the pre-CS period of correct and incorrect trials. The poststimulus phasic response, however, was absent on incorrect trials, suggesting that the stimulus-evoked phasic response of dopamine neurons may relate to stimulus detection. The prestimulus activation of VTA neurons may modulate cortical systems that represent internal states of stimulus expectation and provide a mechanism for dopamine neurotransmission to influence preparatory attention to an expected stimulus.

Importance of unpredictability for reward responses in primate dopamine neurons

1994 ◽  
Vol 72 (2) ◽  
pp. 1024-1027 ◽  
Author(s):  
J. Mirenowicz ◽  
W. Schultz
Keyword(s):  
Single Neuron ◽  
Neuronal Response ◽  
Reaction Time Task ◽  
Dopamine Neurons ◽  
Conditioned Reward ◽  
Central Importance ◽  
Phasic Response ◽  
Single Neuron Recording ◽  
Auditory Reaction Time ◽  
Behaving Monkeys

1. We used single neuron recording techniques in two behaving monkeys to investigate the conditions in which dopamine neurons respond to primary rewarding or potentially rewarding stimuli. Animals received drops of liquid either outside behavioral tasks or as rewards during learning or established performance of an auditory reaction time task. 2. Three quarters of dopamine neurons showed a short-latency, phasic response to liquid that was delivered outside the task without being predicted by phasic stimuli. The same neurons responded to liquid reward during learning but not when task performance was established, at which time the neuronal response occurred to the conditioned, reward-predicting, movement-triggering stimulus. 3. These data suggest that the responses of dopamine neurons to rewarding or potentially rewarding liquid are due to the temporally unpredicted stimulus occurrence. A known, reward-predicting, tonic context does not prevent dopamine neurons from responding to the rewarding liquid. The responses during learning apparently occur because reward is not yet reliably predicted by a conditioned phasic stimulus. Because the unpredicted occurrence of reward is of central importance for learning, these responses allow dopamine neurons to play an important role in reward-driven learning.

Striatal Nitric Oxide Signaling Regulates the Neuronal Activity of Midbrain Dopamine Neurons In Vivo

2000 ◽  
Vol 83 (4) ◽  
pp. 1796-1808 ◽  
Author(s):  
Anthony R. West ◽  
Anthony A. Grace
Keyword(s):  
Nitric Oxide ◽  
Electrical Stimulation ◽  
Substantia Nigra ◽  
Firing Rate ◽  
Dopamine Neurons ◽  
Neuron Activity ◽  
Drug Infusion ◽  
Nitric Oxide Signaling ◽  
Stimulation Of

A major component of the cortical regulation of the nigrostriatal dopamine (DA) system is known to occur via activation of striatal efferent systems projecting to the substantia nigra. The potential intermediary role of striatal nitric oxide synthase (NOS)-containing interneurons in modulating the efferent regulation of DA neuron activity was examined using single-unit recordings of DA neurons performed concurrently with striatal microdialysis in anesthetized rats. The response of DA neurons recorded in the substantia nigra to intrastriatal artificial cerebrospinal fluid (ACSF) or drug infusion was examined in terms of mean firing rate, percent of spikes fired in bursts, cells/track, and response to electrical stimulation of the orbital prefrontal cortex (oPFC) and striatum. Intrastriatal infusion of NOS substrate concurrently with intermittent periods of striatal and cortical stimulation increased the mean DA cell population firing rate as compared with ACSF controls. This effect was reproduced via intrastriatal infusion of a NO generator. Infusion of either a NOS inhibitor or NO chelator via reverse microdialysis did not affect basal firing rate but increased the percentage of DA neurons responding to striatal stimulation with an initial inhibition followed by a rebound excitation (IE response) from 40 to 74%. NO scavenger infusion also markedly decreased the stimulation intensity required to elicit an IE response to electrical stimulation of the striatum. In single neurons in which the effects of electrical stimulation were observed before and after drug delivery, NO antagonist infusion was observed to decrease the onset latency and extend the duration of the initial inhibitory phase induced by either oPFC or striatal stimulation. This is the first report showing that striatal NO tone regulates the basal activity and responsiveness of DA neurons to cortical and striatal inputs. These studies also indicate that striatal NO signaling may play an important role in the integration of information transmitted to basal ganglia output centers via corticostriatal and striatal efferent pathways.

scholarly journals Encoding of speed and direction of movement in the human supplementary motor area

2009 ◽  
Vol 110 (6) ◽  
pp. 1304-1316 ◽  
Author(s):  
Ariel Tankus ◽  
Yehezkel Yeshurun ◽  
Tamar Flash ◽  
Itzhak Fried
Keyword(s):  
Firing Rate ◽  
Supplementary Motor Area ◽  
Motor Task ◽  
Motor Area ◽  
Anterior Cingulate ◽  
Neuron Activity ◽  
Kinematic Parameters ◽  
Speed Increase ◽  
Hand Motion ◽  
Depth Electrodes

Object The supplementary motor area (SMA) plays an important role in planning, initiation, and execution of motor acts. Patients with SMA lesions are impaired in various kinematic parameters, such as velocity and duration of movement. However, the relationships between neuronal activity and these parameters in the human brain have not been fully characterized. This is a study of single-neuron activity during a continuous volitional motor task, with the goal of clarifying these relationships for SMA neurons and other frontal lobe regions in humans. Methods The participants were 7 patients undergoing evaluation for epilepsy surgery requiring implantation of intracranial depth electrodes. Single-unit recordings were conducted while the patients played a computer game involving movement of a cursor in a simple maze. Results In the SMA proper, most of the recorded units exhibited a monotonic relationship between the unit firing rate and hand motion speed. The vast majority of SMA proper units with this property showed an inverse relation, that is, firing rate decrease with speed increase. In addition, most of the SMA proper units were selective to the direction of hand motion. These relationships were far less frequent in the pre-SMA, anterior cingulate gyrus, and orbitofrontal cortex. Conclusions The findings suggest that the SMA proper takes part in the control of kinematic parameters of endeffector motion, and thus lend support to the idea of connecting neuroprosthetic devices to the human SMA.

scholarly journals Transient dopamine neuron activity precedes and encodes the vigor of contralateral movements

2021 ◽  
Author(s):  
Marcelo D Mendonça ◽  
Joaquim Alves da Silva ◽  
Ledia F. Hernandez ◽  
Ivan Castela ◽  
José Obeso ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Neuron Activity ◽  
Similar Proportion ◽  
List Type ◽  
Dopamine Depletion ◽  
Movement Initiation ◽  
Transient Activity ◽  
Forelimb Movement

SummaryDopamine neurons (DANs) in the substantia nigra pars compacta (SNc) have been related to movement vigor, and loss of these neurons leads to bradykinesia in Parkinson’s disease. However, it remains unclear whether DANs encode a general motivation signal or modulate movement kinematics. We imaged activity of SNc DANs in mice trained in a novel operant task which relies on individual forelimb movement sequences. We uncovered that a similar proportion of SNc DANs increased their activity before ipsi- vs. contralateral forelimb movements. However, the magnitude of this activity was higher for contralateral actions, and was related to contralateral but not ipsilateral action vigor. In contrast, the activity of reward-related DANs, largely distinct from those modulated by movement, was not lateralized. Finally, unilateral dopamine depletion impaired contralateral, but not ipsilateral, movement vigor. These results indicate that movement-initiation DANs encode more than a general motivation signal, and invigorate kinematic aspects of contralateral movements.HighlightsDeveloped a freely-moving task where mice learn rapid individual forelimb sequences.Movement-related DANs encode contralateral but not ipsilateral action vigor.The activity of reward-related DANs is not lateralized.Unilateral dopamine depletion impaired contralateral, but not ipsilateral, movement vigor.eTOC summary: Mendonça et al. show that transient activity in movement-related dopamine neurons in substantia nigra pars compacta encodes contralateral, but not ipsilateral action vigor. Consistently, unilateral dopamine depletion impaired contralateral, but not ipsilateral, movement vigor.

scholarly journals Context-dependent multiplexing by individual VTA dopamine neurons

2018 ◽  
Author(s):  
Kremer Yves ◽  
Flakowski Jérôme ◽  
Rohner Clément ◽  
Lüscher Christian
Keyword(s):  
Prediction Error ◽  
Internal Representation ◽  
Dopamine Neurons ◽  
Neuron Activity ◽  
Movement Velocity ◽  
Tonic Firing ◽  
Reward Prediction ◽  
Directed Action ◽  
Operant Task

AbstractDopamine (DA) neurons of the ventral tegmental area (VTA) track external cues and rewards to generate a reward prediction error (RPE) signal during Pavlovian conditioning. Here we explored how RPE is implemented for a self-paced, operant task in freely moving mice. The animal could trigger a reward-predicting cue by remaining in a specific location of an operant box for a brief time before moving to a spout for reward collection. In vivo single-unit recordings revealed phasic responses to the cue and reward in correct trials, while with failures the activity paused, reflecting positive and negative error signals of a reward prediction. In addition, a majority of VTA DA neurons also encoded parameters of the goal-directed action (e.g. movement velocity, acceleration, distance to goal and licking) by changes in tonic firing rate. Such multiplexing of individual neurons was only apparent while the mouse was engaged in the task. We conclude that a multiplexed internal representation during the task modulates VTA DA neuron activity, indicating a multimodal prediction error that shapes behavioral adaptation of a self-paced goal-directed action.

Why Does the Single Neuron Activity Change from Trial to Trial during Sensory-Motor Task?

1997 ◽  
Vol 36 (04/05) ◽  
pp. 322-325
Author(s):  
A. Terao ◽  
T. Hasbroucq ◽  
I. Mouret ◽  
J. Seal ◽  
M. Akamatsu
Keyword(s):  
Neural Network ◽  
Reaction Time ◽  
Single Neuron ◽  
Motor Task ◽  
Reaction Time Task ◽  
Neuron Activity ◽  
Peak Activity ◽  
Neural Connections ◽  
Trial Analysis ◽  
Sensory Motor

Abstract:Single neuron activities from cortical areas of a monkey were recorded while performing a sensory-motor task (a choice reaction time task). Quantitative trial-by-trial analysis revealed that the timing of peak activity exhibited large variation from trial to trial, compared to the variation in the behavioral reaction time of the task. Therefore, we developed a multi-unit dynamic neural network model to investigate the effects of structure of neural connections on the variation of the timing of peak activity. Computer simulation of the model showed that, even though the units are connected in a cascade fashion, a wide variation exists in the timing of peak activity of neurons because of parallel organization of neural network within each unit.

scholarly journals Neurotensin inhibits both dopamine- and GABA-mediated inhibition of ventral tegmental area dopamine neurons

2015 ◽  
Vol 114 (3) ◽  
pp. 1734-1745 ◽  
Author(s):  
Katherine Stuhrman ◽  
Aaron G. Roseberry
Keyword(s):  
Ventral Tegmental Area ◽  
Calcium Release ◽  
Transient Receptor Potential ◽  
Brain Slices ◽  
Receptor Activation ◽  
Dopamine Neuron ◽  
Dopamine Neurons ◽  
Neuron Activity ◽  
Inward Current ◽  
Ventral Tegmental

Dopamine is an essential neurotransmitter that plays an important role in a number of different physiological processes and disorders. There is substantial evidence that the neuropeptide neurotensin interacts with the mesolimbic dopamine system and can regulate dopamine neuron activity. In these studies we have used whole cell patch-clamp electrophysiology in brain slices from mice to examine how neurotensin regulates dopamine neuron activity by examining the effect of neurotensin on the inhibitory postsynaptic current generated by somatodendritic dopamine release (D2R IPSC) in ventral tegmental area (VTA) dopamine neurons. Neurotensin inhibited the D2R IPSC and activated an inward current in VTA dopamine neurons that appeared to be at least partially mediated by activation of a transient receptor potential C-type channel. Neither the inward current nor the inhibition of the D2R IPSC was affected by blocking PKC or calcium release from intracellular stores, and the inhibition of the D2R IPSC was greater with neurotensin compared with activation of other Gq-coupled receptors. Interestingly, the effects of neurotensin were not specific to D2R signaling as neurotensin also inhibited GABAB inhibitory postsynaptic currents in VTA dopamine neurons. Finally, the effects of neurotensin were significantly larger when intracellular Ca2+ was strongly buffered, suggesting that reduced intracellular calcium facilitates these effects. Overall these results suggest that neurotensin may inhibit the D2R and GABAB IPSCs downstream of receptor activation, potentially through regulation of G protein-coupled inwardly rectifying potassium channels. These studies provide an important advance in our understanding of dopamine neuron activity and how it is controlled by neurotensin.

Pharmacological Modulation of the Gating Properties of Small Conductance Ca2+-Activated K+ Channels Alters the Firing Pattern of Dopamine Neurons In Vivo

2010 ◽  
Vol 104 (3) ◽  
pp. 1726-1735 ◽  
Author(s):  
Kjartan F. Herrik ◽  
Palle Christophersen ◽  
Paul D. Shepard
Keyword(s):  
Firing Rate ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Pacemaker Activity ◽  
Sk Channels ◽  
Pharmacological Modulation ◽  
Sk Channel ◽  
Discharge Patterns ◽  
Small Conductance

Dopamine (DA) neurons are autonomous pacemakers that occasionally fire bursts of action potentials, discharge patterns thought to reflect tonic and phasic DA signaling, respectively. Pacemaker activity depends on the concerted and cyclic interplay between intrinsic ion channels with small conductance Ca2+-activated K+ (SK) channels playing an important role. Bursting activity is synaptically initiated but neither the transmitters nor the specific ion conductances involved have been definitively identified. Physiological and pharmacological regulation of SK channel Ca2+ sensitivity has recently been demonstrated and could represent a powerful means of modulating the expression of tonic/phasic signaling in DA neurons in vivo. To test this premise, we characterized the effects of intravenous administration of the novel positive and negative SK channel modulators NS309 and NS8593, respectively, on the spontaneous activity of substantia nigra pars compacta DA neurons in anesthetized C57BL/6 mice. NS309, dose-dependently decreased DA cell firing rate, increased the proportion of regular firing cells, and eventually stopped spontaneous firing. By contrast, systemic administration of the negative SK channel modulator NS8593 increased firing rate and shifted the pattern toward increased irregularity/bursting; an effect similar to local application of the pore blocking peptide apamin. The altered firing patterns resulting from inhibiting SK currents persisted independently of changes in firing rates induced by administration of DA autoreceptor agonists/antagonists. We conclude that pharmacological modulation of SK channel Ca2+-sensitivity represents a powerful mechanism for switching DA neuron firing activity between tonic and phasic signaling modalities in vivo.

scholarly journals Dose-Dependent Switch in Response of Gonadotropin-Releasing Hormone (GnRH) Neurons to GnRH Mediated through the Type I GnRH Receptor

Endocrinology ◽  
2004 ◽  
Vol 145 (2) ◽  
pp. 728-735 ◽  
Author(s):  
Chun Xu ◽  
Xu-Zhi Xu ◽  
Craig S. Nunemaker ◽  
Suzanne M. Moenter
Keyword(s):  
Firing Rate ◽  
Fluorescent Protein ◽  
Brain Slices ◽  
Dose Dependence ◽  
Gnrh Receptor ◽  
Neuron Activity ◽  
Type I ◽  
Pulsatile Release ◽  
Gnrh Neurons ◽  
Green Fluorescent

Abstract Pulsatile release of GnRH provides central control of reproduction. GnRH neuron activity is likely synchronized to produce hormone pulses, but the mechanisms are largely unknown. One candidate for communication among these neurons is GnRH itself. Cultured embryonic and immortalized GnRH neurons express GnRH receptor type I (GnRHR-1), but expression has not been shown in adult GnRH neurons. Using mice that express green fluorescent protein (GFP) in GnRH neurons, we tested whether adult GnRH neurons express GnRHR-1. GFP-positive (n = 42) and -negative neurons (n = 22) were harvested from brain slices, and single-cell RT-PCR was performed with cell contents. Fifty-two percent of the GnRH neurons tested expressed GnRHR-1, but only 9% of non-GnRH hypothalamic neurons expressed GnRHR-1; no false harvest controls (n = 13) were positive. GnRHR-1 expression within GnRH neurons suggested a physiological ultrashort loop feedback role for GnRH. Thus, we examined the effect of GnRH on the firing rate of GnRH neurons. Low-dose GnRH (20 nm) significantly decreased firing rate in 12 of 22 neurons (by 42 ± 4%, P < 0.05), whereas higher doses increased firing rate (200 nm, five of 10 neurons, 72 ± 26%; 2000 nm, nine of 13 neurons, 53 ± 8%). Interestingly, the fraction of GnRH neurons responding was similar to the fraction in which GnRHR-1 was detected. Together, these data demonstrate that a subpopulation of GnRH neurons express GnRHR-1 and respond to GnRH with altered firing. The dose dependence suggests that this autocrine control of GnRH neurons may be not only a mechanism for generating and modulating pulsatile release, but it may also be involved in the switch between pulse and surge modes of release.

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