What are the 2 components of motivation?
Reinforcement and Reward
Some rewards are _____ rewarding/reinforcing
innately
(genetically determined)
Afferents vs Efferents
Afferent: going towards, axons entering a site (affecting cell body)
Efferent: going away from; axons leaving (exiting) a site.
(It takes effort to project away)
How do you trace afferent axons?
Retrograde labeling. Chemicals (Florogold and cholera toxin b) are injected into a nucleus, taken up by terminal buttons and travels to the somas, then you sac the animal, slice and stain brain
How do you trace Efferent Axons?
Anterograde labeling. Chemicals (Lectins) are injected into a nucleus, taken up by dendrites/soma and is transported through axons.
What is the mesolimbic tract?
A dopamine pathway that starts in the VTA (part of the midbrain) and projects to the nucleus accumbens (part of the basal ganglia).
Caudate-Putamen is also called? Is a part of? is involved in (2) ?
Caudate-Putamen is also called the dorsal striatum.
It is part of the basal ganglia.
It regulates movement (plans and modulates movement pathways) and is involved in habit learning, (procedural learning relating to routine behaviors)
Nucleus Accumbens is also called? Is part of? is a gateway for? is involved in?
Nucleus Accumbens is also called the ventral striatum
It is the gateway for cortical and limbic information to enter motor circuitry of the basal ganglia
It regulates motivated behavior and is the site of addiction pathology.
Stroke in the ____ caused patient to become abstinent from nicotine and alcohol (lifelong addict)
dorsal striatum (caudate-putamen)
Integration: Dopamine-Glutamate interactions
95% of __(place)___ neurons are medium ____ ____ neurons. They are of what NT? What do they integrate?
95% of striatal neurons are medium spiny projection neurons. They are GABAergic.
The spiny neurons integrate dopamine from VTA and Glutamate from cortex.
All abused drugs activate the ______ _______ system. Are they the same or different mechanisms?
All abused drugs activate the mesolimbic dopamine system. They do so through different mechanisms
DA and reward
-In NAc, DA lesions or antagonist ____ drug self administration. (only when ___ is high, which suggest it is involved in _____)
-In VTA, DA lesions or antagonist ____ drug self administration
In NAc, Blocking DA decreases self admin. But only when cost (higher lever presses) is high, which suggests it is involved with overcoming motivational costs for completing tasks
In VTA agonist/lesion also reduces self admin.
DA: liking vs. wanting
- Gaping after sucrose was not affected by lesions to the DA system (pleasure/liking), which led to a series of experiment that determined DA is _____________________________
- Is dopamine involved in approach (incentive salience,
DA is not involved in hedonic value (liking)
Nor is it involved in approach/ incentive salience. (study where the hooked up rat to heroin-hallway and measured times: times did not decrease until the day after DA antagonist)
DA's role is in reinforcement
Changes in VTA DA release in response to cues paired with reward:
DA does what when
- there is no cue
-the cue is conditioned and they receive reward
-the cue is conditioned and they receive no reward
- high increase of dopamine after reward without cue
- with cue, there is a high increase in DA after cue but not after the reward.
-Still a high increase of DA after stimulus but a huge lacking later when there is no reward administered.
What is the reward prediction error hypothesis? What is a positive/negative error? What happens with a fully predicted reward?
Dopamine responds to the difference between experienced and anticipated reward.
Positive prediction error: an activation caused by unpredicted reward
Fully predicted reward elicits no response
Negative prediction error: a depression caused by a omission o
-- contrast to prediction error hypothesis--
2 human imaging studies provide evidence for a link between DA and ______
What were the 2 studies measuring?
DA and drug "high" (this is in contrast to prediction error hypothesis)
They gave subjects amphetamines and measure either DAT or D2/D3 binding using PET scans and DA binding correlated with self-reported high
Roles of Dopamine in motivation? (3)
1) DA release
promotes learning
and
developing behavioral strategies
. It compares the expected outcome to actual outcome
2) DA promotes
attention
(e.g. towards cues associated with reinforcement)
3) Excessive dopamine release by addictive drugs causes
ov
A polymorphism in ___ receptor causes _______
-Produces a reward deficit (drugs fill the hole)
-Humans report thrill seeking
-Present in 70% of addicts; 42% of non addicts
D2 receptor polymorphism (Taq1 A1 D2) causes reduced function.
Subjects have increased/decreased D2 binding following cocaine abuse?
decreased
Ventral Pallidum and Addiction
What is called the "final common pathway"?
What is the VP involved with in regards to addiction?
final common pathway: NAc to VP projection (VP is also part of the basal ganglia)
NAc integrates information (DA/Glu), VTA/PFC/amygdala/hippocampus and tells the VP "go" or "nogo"
VP is responsible for motor output
Hippocampus and addiction
HC Modulates firing in? (2)
What 3 things is HC responsible for (that have importance to addiction)?
Inactivation prevents ____ _____ ________
-HC modulates firing in VTA and NAc
-important in memory consolidation, spatial memory and drug-taking context
- inactivation prevents context-primed reinstatement
Amygdala and addiction
Consolidates _______-______ associations
inhibition prevents?
Lights up during imaging of addicts when?
Amygdala consolidates stimulus-reward associations
inhibition prevent the ability of drug cues to elicit drug seeking in reinstatement model
Lights up when addicts are shown drug-associated cues
Dorsolateral PFC is involved with? Damage produces?
dlPFC is involved with working memory (among other things) and produces perseverative or disorganized behavior, especially when new or unfamiliar responses must overcome previously learned ones.
What is the guided activation theory (in regards to PFC)?
PFC neurons alter activity in other brain areas so that appropriate sensory, memory and motor circuits are activated to guide behavior.
Go and stop circuits
What is the Go circuit?
What is the Stop Circuit?
Both are Prefrontal Circuits
GO:
Anterior Cingulate Cortex (
prelimbic PFC
) sends Glu-----> accumbens
core
------> behavioral activation
STOP:
Orbital Cortex (
Infralimbic PFC
) sends Glu------> accumbens
shell
sends GABA------> behavioral inhibition.
The insula is a portion of the __(place)____ often activated during _______
Insula is a portion of cortex often activated during emotional processing.
Phineas Gage had damage to his ______ ___ ______ which produced _________
This provides evidence for?
Phineas Gage damaged his ventromedial prefrontal cortex (where the orbital cortex is) which produced erratic behavior (loss of impulse control). Evidence for stop circuit
drug addicts show altered activity in ventral orbitofrontal cortex indicating loss o
The medial Prefrontal cortex is further divided into (2)? What do they do?
1) Dorsal mPFC: modification of behavior over time
2) Ventral mPFC: behavioral flexibility in response to internal states and external cues
Inactivation of PFC prevents ___ increase but not ____
Inactivation of PFC prevents Glu increase but not DA
What 2 ways can we attenuate relapse by manipulating Glu?
Inhibiting postsynaptic Glu binding (mGluR5, AMPA) attenuates reinstatement to nicotine, cocaine and alcohol.
Agonists at Glu autoreceptors (mGluR2/3)
Glutamate is a critical modulator of _________
neuroplasticity (learning)
We observe impaired ____ and ____ in the ____(place)_____ following cocaine SA and extinction
Impaired LTP and LTD in NAc
What are some evolutionary reasons for lots of dopamine and continued cortical development throughout adolescence? (3)
Why are these also bad? (3)
Reason:
-increased exploration and info gathering
-increased ability to adapt behavior to enviorment
-facilitates social interactions
But they are more easily addicted because
-less sustained focus
-more impulsive
-more responsive to stress
Review of circuitry:
The VTA projects __(NT)___ where (2)?
PFC projects __(NT)__ where (2)?
Hippocampus projects __(NT)__ where (1)?
Amygdala projects __(NT)____ where (1)?
NAc projects ___(NT)____ where (1)?
VTA projects DA to the PFC and NAc
PFC projects Glu to the NAc and the VTA
- Executive control, Go/NoGO, drug paired cues
Hippocampus projects Glu to NAc
- Memory consolidation and drug taking context
Amygdala projects Glu to NAc
-encodes
stimulus-reward
What did the study with yoke cocaine, yoke saline, and a SA group conclude?
They implanted a microdialysis probe in the NAc and measured Glu and DA in reinstatement
Glu is important in relapse (high Glu in relapse) but DA didn't budge
In abstinence states we observe a _____ of PFC. This means.....
In abstinence we observe hypofrontality of PFC. This means that less Glu in NAc and when you relapse Glu is supa freakin high
What are the roles of xct, GLT1, mGluR2/3 in the PFC ---> NAc synapse?
GLT1: Is a transporter on glia that takes glutamate into the glia
xct: a transporter on glia that takes in cysteine and pumps on Glu.
mGluR2/3: an autoreceptor on the pre-synaptic terminal that "brakes" Glu release
How do we attenuate relapse by manipulating Glu? (3)
Inhibiting post-synaptic glutamate binding (
mGluR5 or AMPA
)
Agonists at Glu autoreceptors (mGluR2/3)
Drugs that upregulate xct and GLT-1