Mesolimbic dopamine system and reward

dopamine circuitry

L-tryosine-> L-Dopa -> Dopamine

Fast Scan Cyclic Voltammetry (FSCV)

Measures real-time DA neurotransmission in a specific brain region and in response to specific cues and/or events using electrochemistry Carbon fiber electrode to measure neurotransmitter release Voltage is applied to the fiber to oxidize neurotransmitters It is not selective for neurotransmitters so you have to record at a site you are confident has one type Oxidation (removing 2 electrons) causes current flow DA is oxidized then reduction back to DA Current flow is transformed into concentration of DA (DA) you ultimately get a read of (DA)

In MDP VTA->

NAcc

Ventral Striatum (VS) includes

Nucleus accumbens (NAC) Olfactory tubercle

Rats show individual differences in response to stimuli

Population of goal-trackers and sign-trackers These differences are heritable and related to distinct neural substrates

Pleasure centers gave rise to dopamine pleasure hypothesis

Proposed by roy wise Dopamine junctions represent a synaptic way station .. where sensory inputs are translated into hedonic messages we experience as pleasure euphoria or yumminess Later roy stated : I no longer believe that the amount of pleasure felt is proportional to the amount of dopamine floating around in the brain

2 dorsal striatum

Putamen (Dorsolateral Striatum) Caudate (dorsal medial striatum)

DA activity id necessary for acquisition and performance of

ST but only performance of GT

Midbrain DA neurons response to reward Shultz

Schultz measured spiking of dopamine neurons in VTA in awake behaving monkeys 75-80% of midbrain dopamine (DA) neurons displayed short phasic activation or deactivation to different stimulus events

nigrostriatal dopamine pathway

Set of dopamine neurons with somas in the substantia nigra and axons terminating in the basal ganglia one of two major dopamine pathways; damaged in Parkinson's disease

septal area

Structure in the brain's limbic system that plays a role in the experiencing of pleasure

Gen et al 2010 study

Taught rats to distinguish between benefits and costs Gan et al looked at dopamine release in the nucleus accumbens (NAC) using Fast-Scan cyclic voltammetry (FSCV)

Positive prediction error

This is more/ better than I expected

DA response to reward method

US sugarwater, CS tone Recording from VTA dopaminergic neurons

Scheme of learning by RPE schultz

Use prediction -> receive outcome-> error or keep prediction unchanged -> update prediction if necessary

in drug free test (no Systematic flupenthixol)

acquisition (learning) of ST but not GT was blocked

Liking measured though

affective taste reactivity - Clear facial expressions for sweet and bitter tastes

Higher reward value is encoded by

an increase in DA response

Goal and sign tracking in the lab Sign-tracking response

animal approaches cue (even though this does not cause reward delivery)

Goal and sign tracking in the lab Goal-tracking response

animal approaches receptacle (even though reward has not been delivered yet)

Rats selectively bred for differences in locomotor responses to novel environment Low-reactive (bLR) rats

become goal trackers

Rats selectively bred for differences in locomotor responses to novel environment High-reactive (bHR) rats

become sign trackers

Gan et al 2 trial types Free choice trials

both option are available rats pick whatever options they want cue turns bove both levers

Liking and wanting systems both interact with

cannabinoids

other studies DO find NAC especially the core tracks

cost

Gen et al 2010 study benefits

different amounts of pellets

Gen et al 2010 study costs

different amounts of presses

Systematic flupenthixol

disrupts expression of sign tracking and goal tracking throughout training

Nonselective Da receptor antagonist

disrupts sign tracking

Wanting mediated by

dopamine system

Projections terminate in (NDP)

dorsal striatum (DS)

Liking

hedonic reactions to rewards/outcomes. Experienced as an implicit behavior. Liking without quotation marks is the conscious form related to feeling of pleasure

Heath 1972 study results

humans pressed a button for stimulation in the septal area Patient B-19 in one case experiences strong sexual urges as a result

results : Reward prediction error Reward underpredicted

increased DA response, expectation of reward increases

DA release was measured in the core of nucleus accumbens using FSCV during conditioning for food Sign tackers (bHR) show

increasing phasic DA responses to CS and decreasing responses to US over training Hallmark of prediction error

DA release was measured in the core of nucleus accumbens using FSCV during conditioning for food GOal-trackers (bLR)

maintain phasic responses to US throughout training

Wanting measured through

motivation - increased food intake - excessive behavior towards a stimulus Ex CS

results : Reward prediction error Reward fully predicted

no change in DA activity, no reward-related learning

Build expectation (Positive RPE)

now I know what this will do

Gan et al 2 trial types Forced choice trials

only 1 option is available rats learned to respond on a lever when a light cue is on

Liking mediated by

opioid system

results of olds and Milner study

rats lever pressed for stimulation of septal area So potent hungry rats would press for stimulation instead of press for food

Olds and Milner located reward centers in the brain structure known as the

septal area

DA neurotransmission is necessary for

sign tracking

hedonic hotspots are

sites are anatomically dissociable from wanting hot spots

Source of dopamine in NDP

substantia nigra (SNc)

reward prediction error

the difference between the actual reward received versus the amount of predicted or expected reward The degree which one receives more or less reward than predicted

Wanting aka incentive salience

the process of stimuli gaining motivational value. Stimuli become motivational magnets that attracts behavior. Wanting without quotation marks is the cognitive form, thinking of the goal you desire and how to attain it

Intracranial self-stimulation (ICSS)

the repeated performance of a response that delivers electrical stimulation to certain sites in the animal's brain Electrical stimulation of brain areas like medial forebrain bundle (MFB) support lever-pressing behavior

Negative prediction error

this is less/ worse than what I expected

NAC DA is more sensitive to

value than cost

Projections terminate in (MDP)

ventral striatum (VS)

Source of dopamine in MDP

ventral tegmental area (VTA)

Neuroscientists now distinguish liking from

wanting

Drug addiction is seen as dysfunction of

wanting system and not liking system

hedonic valence

('liking'/'disliking') hotspot

Cost manipulation

- rats are good at choosing the low cost less presses option - DA cue reactivity shoes a temporary effect in 16v2 and not effect in 16 v 32 - not good at tracking cost

Benefit manipulation

- rats are good at identifying the high benefit (more pellets) option - they'll choose optimally

DA neurons in the mesolimbic pathway encode economic value

- reward magnitude - delay discounting - probability - uncertainty

Gan et al methods Recording DA activity forced choice

- voltammetry probe was implanted in the nucleus accumbens - activity was to the cue only not the choice or reward

Gan et al methods Benefit vs cost conditions

-in the benefit condition 16 lever presses lead to either smaller or larger amounts of pellets -Same cost different amount - in the cost condition less or more lever pressures lead to 1 pellet - same amount different cost

Hedonic hotspot in the NAcc is about

1/10 the volume of NAcc

medial forebrain bundle (MFB)

A fiber bundle that runs in a rostral-caudal direction through the basal forebrain and lateral hypothalamus; electrical stimulation of these axons is reinforcing Involved in rewarding behavior Stimulating MFB produces strong lever pressing behavior Self stimulation of the MFB directly activates ascending and descending fibers Some models suggest descending fibers could interact with ascending fibers

Sign tracking In pavlovian conditioning

CS causes conditioned response to the CS itself (lever). CS gains incentive salience. It attracts behavior towards itself ex: game cues in gambling themselves become wanted

goal tracking In pavlovian conditioning

CS causes conditioned response to where a US is delivered

Liking dissociated form wanting

Can be experienced separately You can want something but not necessarily like it Ex smoking may not like the smell but want the smoke more

Goal and sign tracking in the lab

Cue signals upcoming delivery reward (8 second lever insertion and cue light) Cues terminate reward delivered : animal approaches receptacle

results : Reward prediction error Reward overpredicted

DA response decreased, expectation of reward decreased

In NDP Sec->

DS

Olds and Milner Study

Demonstrated existence of pleasure center in the brain using "self-stimulation" studies in rats electrode was placed in the septal area electric surges often induced dopamine release ICSS of septal area

MDP reward/ motivation pathway

Dopamine neuron originate in VTA and terminate in ventral striatum Reminder : MFB medial forebrain bundle spans this pathway Regulates motivation, reward value, etc

mesolimbic dopamine pathway

Dopamine neurons with somas in the ventral tegmental area and axons terminating in the limbic system one of two major dopamine pathways; may be involved in psychotic reactions and in drug reward

Some issues with liking and wanting distinction

Dopamine systems interact with opioids Opioids can modulate the addictive properties of drugs

Heath 1972 study

Humans Electrode was placed in the septal area ICSS of septal area

Learned expectation (No RPE)

I know what will happen

No expectation RPE

I wonder what this will do