How does association of fear arise?
-long-term potentiation in the amygdala
What was the rat experiment with self-stimulation?
-certian regions of the brain if stimulated give rise to pleasure -sites in the brain that can directly provide the reward -when pushes the lever then reinforcment -rather push that than anything else -highly motivated behaviour of the brain
What were the sites in the rat brain that were stimulated by the self-stimulation experiment?
-there were many sites but falling along the same bit 1:-most common lateral hypothalamus 2:-basal forebrain=nucleus Accumbens 3:-medial prefrontal cortex, -other regions in the forebrain 4:-then midbrain: (VTA) ventral tegmental area -all along a pathway from the midbrain through the basal forebrain to the prefrontal cortex
What is the pathway of the self-stimulation activation?
-path from ventral medial forebrain to the rostral brainstem, centred around a fibre tract called the median forebrain bundle
What are the fibres running from the VTA to the basal forebrain and medial prefrontal cortex called?
-median forebrain bundle -it is a key structue
What is the median forebrain bundle important for?
-key structure when you want to induce the self stimulation behaviour -it goes from the VTA to nucleus accumbens (part of the basal ganglia) and to prefrontal regions
What is the VTA a source of?-
- the ventral tegmental area is a source (via the median forebrain bundle) of dopamine to prefrontal cortex and associated basal ganglia regions (nucleus accumbens)
What do some hedonic drugs such as opiates facilitate in the VTA?
-release of dopamine by VTA neurons on frontal regions
What do some dopaminergic agonists do?
-e.g. amphetamines -powerful elevators of mood
What are the neurons of the VTA like?
-dopaminergic -VTA is in the midbrain
Where do the VTA neurons project to?
-nucleus acumbens (basal ganglia) -prefrontal regions
What is the pathway involved in addictive behavior in a rat?
What is the pathway involved in addictive behavior in a human? (the dopamine system)
What is the VTA like? Size etc.
-relatively small nucleus -large neurons that are fairly scattered in the nuclear region -have projections that are highly divergent -each of the neurons has contact with hundreds and thousands of other neurons in the prefrontal cortex or accumbens -type of synapse is: en passant type, varacose endings -dopamine that is released has modulatory effect, subtly changes their excitability
What is the limbic loop like?
What is the limbic loop like in detail?
Where is the VTA?
-in the midbrain
-next to substantia nigra
AT which sites can drugs act to increase the activity of the limbic loop?
-at VTA -at nucleus accumbens (ventral striatum)
How do opiates act? (non addicted)
-increasing VTA activity, inhibit GABAercgic neurons so VTA is more active (released from inhibition) so more dopamine-probably also act on nucleus accumbens
How do cocaine and amphetamine act? (non addicted)
-cocaine and amphetamine= increse the dopamine allowed in the synapse
-between the VTA and accumbens
How is behaviour of a person affected when taking drugs?
-if take drugs the behaviour that is reinforced is the taking of drugs -the other behaviours that used to make you happy not as much anymore -then becomes the only thing that activates this pathway --become sensitised,= more ready to produce dopamine, only to the drug though, the drug induced dopamine ---become less sensitive to the gluatamtergic inputs coming from cortex, cingulate, amygdala etc., normally presenting our goals and what mediates us
What is meant by hypofrontal?
-in addicted individuals, don't care about what we are normally intersetd in -long term goals, no longer matter as much -lose the behaviour that motivates normal individuals -the only goal is getting the drug -the drug effect becomes less pronounced over time, the pleasure, the getting and obtaing it is more important that the effect of taking it at some point -the pleasure state not long tern
What happens in the VTA of an addicted person?
(the left= VTA)
- the neurons in VTA become more sensitive to inputs, the tyrosine hydroxylase (enzyme that is part of the pathway that makes dopamine) is upregulated
-glutamate receptor that respons to input is regulated
-transcription factor is upregulated the CREB,
-become sensitised,= more ready to reduce dopamine, only to the drug though, the drug induced dopamine
-----become less sensitive to the gluatamtergic inputs coming from cortex, cingulate, amygdala etc., normally presenting our goals and what mediates us
What happens in the nucleus accumbens of an addicted person?
in the accumbens also see changes in gene transcription:FosB= transcription factor
-also second messenger pathway that change excitability pathways
-become less sensitive to inputs from cortex, more sensitive to drug induced
What was the difference in the self-stimulation experiment in humans?
-self-stimulation of dopaminergic pathways: reports from self-stimulating humans suggests mental state of expecting pleasure to happen, anticipation of potential rewarding state -not reward itself -addictive behaviour may relate to reward or the anticipatory state but seems to be dopaminergic
What was the experiment with rats to see of the dopaminergic pathways are reward or wanting reward?
-looking at if there is a difference in the wanting or enjoying -experiment :kill dopaminergic neurons in rats= effect they don't respond to the lever thing anymore, they do nothing they don't even eat= get thinner and thinner -if you give them food, then show behaviour as if experience sth pleasurable -if give sth unpleasant then react the same way as everyone else -so dopamine not about pleasure it is about wanting pleasure, seeking things, rather than enjoying them
What is the VTA neuron activity when reward delivered?
-reward delivered, after then there is VTA activity
What is the VTA neuron activity when conditioned with the light signaling reward?
-if you conditioned it-
if light and you push= the quickly learn to associate the light with reward
-then dopamine before the reward, now it is at the signal of the reward= the light
-the likelyhood that you will get a reward
What is the VTA neuron activity when conditioned for the reward signal and then receive no signal?
- then keep going and no reward-
-then if do not get reward the VTA is supressed
-so VTA behaves like a predictor of reward, not reward itself
How can reward undermine motivation?
-dopamine tells you about whether or not you will get pleasure -two groups one rewarded, one nonrewarded -both have the same activity in the first session -in the second session -non-reward do the same as before -reward told they won't get money= they have no representation in the forebrain, -they don't care -taking away reward= will demotivate -also most effcient if non regular rewarding, if you keeop a chance of reward
What is dopamine if it is not reward or pleasure?
dopamine is a fact about how likely a reward is
-reward prediction error can be calculated (neuroeconomics)
-dopamine over time is a function of=how much reward you actually got, and discounted predicted reward (how much you value sth given now vs later)
What are the diffuse modulatory systems of the central nervous system that are often sites of drug action? (general characteristics of the systems that drugs act on)
1. A nucleus or cluster of nuclei with relatively few neurons (thousands rather than millions) 2. Most of the nuclei are in the central core of the brain: the brainstem and basal forebrain 3. Each neuron can influence many (maybe hundreds of thousands) of neurons elsewhere in the brain- this is called a highly divergent projection 4. The synapses made by these cells are typically en passant
What is an en passant synapse?
-synapse occurring along the length of the axon (en passant). -synaptic junctions appear partway along an axon as it extends
What is unusual in the dopamine system?
-dopamine is unusual, restricted in projections more than the others
What is the norepinephrine system like?
noreginergic neurons = the green blob
-called locus coeruleus
-small number of neurons
What is the serotonin system like?
-seritonergic group projects everywhere
What is the acetylcholine system like?
-acteinerggic also projects everywhwere
-all these nuclei are important in global behaviour
How do the drugs work and where do they act on?
this is where the drugs work on
-if change the amout of transmission
-diffusion system cocaine and amphetamine= stopping the reuptake of NE and DE, so it takes longer for reuptake
-so more in the synapse
-Is dopamine pleasure or reward? -dopamine does other things and other agents affect reward and motivation -the underlying cause of behaviour in experimental animals is difficult to ascribe -dopamine's locus of action is broad (divergent projections) -self-stimulation at high rates is not associated with concomitantly high levels of dopamine release -dopamine depletion leads to anehedonia but does not eliminate behaviours associated with pleasurable and aversive experiences