Firing modes of midbrain dopamine cells in the freely moving rat

Hyland, Brian I.; Reynolds, John N. J.; Hay, Jeremy E; Perk, Christopher G.; Miller, Richard J.

doi:10.1016/s0306-4522(02)00267-1

Cited by 448 publications

(497 citation statements)

References 82 publications

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“…As nicotine preferentially filters the dopamine signal resulting from lower tonic activity, it could enhance the dopamine response due to salient stimuli that evoke burst firing [26]. Such contrast enhancement between tonic and phasic activity might help to elucidate the underlying mechanism of nicotineinduced behavioral sensitization and the development of addiction disorders.…”

Section: Discussionmentioning

confidence: 99%

Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum

et al. 2016

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Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500nM) induced a decrease in dopamine efflux at low frequency (single pulse or 5 pulses at 10Hz) and an increase at high frequency (100Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.

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Section: Discussionmentioning

confidence: 99%

Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum

et al. 2016

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“…Stimuli consisted of either single pulses (1 pulse, p) or bursts of pulses (2-5 p) at a physiological range of DA neuron firing frequencies which included 'tonic' rates (1-10 Hz) and 'phasic' burst frequencies (25-100 Hz) that mimic the firing patterns of DA neurons that accompany 'reward-related' events in vivo eg the presentation of primary reward, a conditioned reinforcer or rewardpredictor (Bayer and Glimcher, 2005;Hyland et al, 2002;Schultz, 1986). The term 'burst sensitivity' refers to the relative sensitivity of DA release to a burst vs a single pulse and denotes the ratio of release by a 4 p burst vs 1 p.…”

Section: Experimental Design and Analysismentioning

confidence: 99%

“…Changes in dopaminergic firing frequency within a burst are critical to the processing of reward-related information: Typically, low-frequency activity (0.5-5 Hz) is associated with nonreward-related activity, while high frequencies (20-100 Hz) signal reward-related information (Hyland et al, 2002;Schultz, 1986Schultz, , 2002. We have previously shown that nAChRs critically govern how DA is released by different frequencies of presynaptic activity and that nAChR desensitization by nicotine changes this frequency filtering (Rice and Cragg, 2004;Zhang and Sulzer, 2004).…”

Section: A6b2*-nachrs Can Account For All Frequency Filtering Of Da Rmentioning

confidence: 99%

α6-Containing Nicotinic Acetylcholine Receptors Dominate the Nicotine Control of Dopamine Neurotransmission in Nucleus Accumbens

Exley

Clements

Hartung

et al. 2007

Neuropsychopharmacol

227

262

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Modulation of striatal dopamine (DA) neurotransmission plays a fundamental role in the reinforcing and ultimately addictive effects of nicotine. Nicotine, by desensitizing b2 subunit-containing (b2*) nicotinic acetylcholine receptors (nAChRs) on striatal DA axons, significantly enhances how DA is released by reward-related burst activity compared to nonreward-related tonic activity. This action provides a synaptic mechanism for nicotine to facilitate the DA-dependent reinforcement. The subfamily of b2*-nAChRs responsible for these potent synaptic effects could offer a molecular target for therapeutic strategies in nicotine addiction. We explored the role of a6b2*-nAChRs in the nucleus accumbens (NAc) and caudate-putamen (CPu) by observing action potential-dependent DA release from synapses in real-time using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in mouse striatal slices. The a6-specific antagonist a-conotoxin-MII suppressed DA release evoked by single and low-frequency action potentials and concurrently enhanced release by high-frequency bursts in a manner similar to the b2*-selective antagonist dihydro-b-erythroidine (DHbE) in NAc, but less so in CPu. The greater role for a6*-nAChRs in NAc was not due to any confounding regional difference in ACh tone since elevated ACh levels (after the acetylcholinesterase inhibitor ambenonium) had similar outcomes in NAc and CPu. Rather, there appear to be underlying differences in nAChR subtype function in NAc and CPu. In summary, we reveal that a6b2*-nAChRs dominate the effects of nicotine on DA release in NAc, whereas in CPu their role is minor alongside other b2*-nAChRs (eg a4*), These data offer new insights to suggest striatal a6*-nAChRs as a molecular target for a therapeutic strategy for nicotine addiction.

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“…Chloral hydrate was utilized since, under this anesthetic, DA neuron activity states more closely resemble that observed in freely moving rats (Hyland et al, 2002). Anesthesia was maintained by supplemental administration of chloral hydrate as required to maintain suppression of limb compression withdrawal reflex and a core body temperature of 371C was sustained by a thermostatically controlled heating pad.…”

Section: Surgery and Pharmacological Manipulationsmentioning

confidence: 99%

The Hippocampus Modulates Dopamine Neuron Responsivity by Regulating the Intensity of Phasic Neuron Activation

Lodge

Grace

2005

Neuropsychopharmacol

233

225

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Aberrant dopamine (DA) signaling has been advanced as a contributing factor to the pathophysiology of a number of psychiatric conditions including schizophrenia; however, the many factors involved in regulating DA system responsivity have not been completely delineated to date. We have shown previously that DA neuron activity states are independently regulated by distinct afferent pathways. We now provide evidence that these pathways interact to control the population of neurons that are phasically activated. As shown previously, infusions of NMDA into the ventral subiculum (vSub) increases the number of spontaneously active DA neurons (population activity), while having no effect on firing rate or average bursting activity. In contrast, NMDA activation of the pedunculopontine tegmental nucleus (PPTg) results in a significant increase in DA neuron burst firing without significantly affecting population activity. However, simultaneous excitation of the vSub and PPTg induces a significant increase in both DA neuron population activity and burst firing resulting in a B4-fold increase in the number of high-bursting neurons observed per electrode track. These data suggest that DA neuron population activity is not simply associated with the tonic release of DA in forebrain regions, but rather represents a recruitable pool of DA neurons that can be further modulated by excitatory inputs to induce a graded phasic response. Taken as a whole, we propose that the synchronous activity of distinct afferent inputs to the VTA phasically activates selective populations of DA neurons, and hence may be a site of pathological regulation underlying aberrant DA signaling.

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Firing modes of midbrain dopamine cells in the freely moving rat

Cited by 448 publications

References 82 publications

Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum

Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum

α6-Containing Nicotinic Acetylcholine Receptors Dominate the Nicotine Control of Dopamine Neurotransmission in Nucleus Accumbens

The Hippocampus Modulates Dopamine Neuron Responsivity by Regulating the Intensity of Phasic Neuron Activation

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