Bidirectional Control of Alcohol-drinking Behaviors Through Locus Coeruleus Optoactivation.

The relationship between stress and alcohol-drinking behaviors has been intensively explored; however, neuronal substrates and neurotransmitter dynamics responsible for a causal link between these conditions are still unclear. Here, we optogenetically manipulated locus coeruleus (LC) norepinephrine (NE) activity by applying distinct stimulation protocols in order to explore how phasic and tonic NE release dynamics control alcohol-drinking behaviors. Our results clearly demonstrate contrasting behavioral consequences of LC-NE circuitry activation during low and high frequency stimulation.

Opposite Consequences of Tonic and Phasic Increases in Accumbal Dopamine on Alcohol-Seeking Behavior.

Despite many years of work on dopaminergic mechanisms of alcohol addiction, much of the evidence remains mostly correlative in nature. Fortunately, recent technological advances have provided the opportunity to explore the causal role of alterations in neurotransmission within circuits involved in addictive behaviors. Here, we address this critical gap in our knowledge by integrating an optogenetic approach and an operant alcohol self-administration paradigm to assess directly how accumbal dopamine (DA) release dynamics influences the appetitive (seeking) component of alcohol-drinking behavior.

Real-Time Accumbal Dopamine Response to Negative Stimuli: Effects of Ethanol.

Activity in the mesolimbic dopamine (DA) pathway is known to have a role in reward processing and related behaviors. The mesolimbic DA response to reward has been well-examined, while the response to aversive or negative stimuli has been studied to a lesser extent and produced inconclusive results. However, a brief increase in the DA concentration in terminals during nociceptive activation has become an established but not well-characterized phenomenon.

Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors.

Recent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats.

Real time adenosine fluctuations detected with fast-scan cyclic voltammetry in the rat striatum and motor cortex.

Background: Adenosine serves many functions within the CNS, including inhibitory and excitatory control of neurotransmission. The understanding of adenosine dynamics in the brain is of fundamental importance. The goal of the present study was to explore subsecond adenosine fluctuations in the rat brain in vivo.

Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration.

There is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA) dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive.

Terminal effects of optogenetic stimulation on dopamine dynamics in rat striatum.

In this study, the first in-depth analysis of optically induced dopamine release using fast-scan cyclic voltammetry on striatal slices from rat brain was performed. An adeno-associated virus that expresses Channelrhodopsin-2 was injected in the substantia nigra. Tissue was collected and sectioned into 400μm-thick coronal slices 4 weeks later.

Aversive stimulus differentially triggers subsecond dopamine release in reward regions.

Aversive stimuli have a powerful impact on behavior and are considered to be the opposite valence of pleasure. Recent studies have determined some populations of ventral tegmental area (VTA) dopaminergic neurons are activated by several types of aversive stimuli, whereas other distinct populations are either inhibited or unresponsive. However, it is not clear where these aversion-responsive neurons project, and whether alterations in their activity translate into dopamine release in the terminal field.

Speedball induced changes in electrically stimulated dopamine overflow in rat nucleus accumbens.

Cocaine/heroin combinations (speedball) induce a synergistic elevation in extracellular dopamine concentrations ([DA](e)) in the nucleus accumbens (NAc) that can explain the increased abuse liability of speedball. To further delineate the mechanism of this neurochemical synergism, in vivo fast-scan cyclic voltammetry (FSCV) was used to compare NAc DA release and reuptake kinetic parameters following acute administration of cocaine, heroin and speedball in drug-naïve rats. These parameters were extracted from accumbal DA overflow induced by electrical stimulation of the ventral tegmental area.

Optogenetic control of striatal dopamine release in rats.

Optogenetic control over neuronal firing has become an increasingly elegant method to dissect the microcircuitry of mammalian brains. To date, examination of these manipulations on neurotransmitter release has been minimal. Here we present the first in-depth analysis of optogenetic stimulation on dopamine neurotransmission in the dorsal striatum of urethane-anesthetized rats.

Real-time voltammetric detection of cocaine-induced dopamine changes in the striatum of freely moving mice.

In the present voltammetric study, we have characterized cocaine-induced changes in evoked dopamine release and uptake in the striatum of freely moving mice in real time. Cocaine induced marked dopamine uptake inhibition measured as apparent K(m) changes, producing a maximal effect 20min following a single injection (15mg/kg, i.p.

Dopamine uptake changes associated with cocaine self-administration.

The present study was designed to reveal the relationship between cocaine-induced dopamine uptake changes and patterns of cocaine self-administration observed under a fixed-ratio schedule. Cocaine was intravenously infused into anesthetized rats, according to inter-infusion intervals obtained from self-administering animals, and dopamine uptake changes (apparent K(m)) were assessed in the nucleus accumbens using voltammetry. The data demonstrate that cocaine-induced dopamine transporter (DAT) inhibition accounts for the accumbal dopamine fluctuations, which are associated with the cyclic regularity of cocaine intake observed during self-administration.

Nonlinear motion of optically torqued nanorods.

We apply light torques to single optically trapped glass nanorods suspended in water. The resulting motion is studied experimentally and consists of two distinct regimes: a linear regime where the rod angle increases linearly with time and a nonlinear regime where the rod angle changes nonlinearly, experiencing accelerations and rapid reversals. We present a detailed theoretical treatment for the motion of such nanorods, which agrees extremely well with the observed motion.

Absolute two-photon cross section of Rb measured by differential absorption.

We applied a simple, sensitive differential absorption technique to measure the two-photon cross section for the 5(2)S((1/2))(F(g) = 2) ? 5(2)D(5/2)(F(e) = 4) hyperfine transition in (85)Rb [sigma((2)) = (1.2 +/- 0.5) x 10(-18) cm(4)/W].

Simple diffuser for production of laser speckle.

A passive optical element that is a simple, inexpensive, and effective way for producing laser speckle is described. The optical element, a random phase plate, was developed in our laboratory. The statistics of the speckle pattern it produces were measured and are discussed in this paper.