Neuroanatomy 2 Flashcards
How would you explain “diffuse modulatory systems”? Why would it be useful to study them?
= monoamine and acetylcholine systems that project ascending connections from the brainstem to the entire cortex
- excert modulatory power (alone cannot do much)
- implicated in major neuropsychiatric disorders
What steps could be visible within emotional circuit of the brain? Which brain areas are responsible?
- Detection of environmental stimuli
- senses, thalamus
- Quick interpretation
- hippocampus, amygdala
- Evaluation of these signals
- Prefrontal cortex, Nucleus accumbens
- Action Preparation
- Motor cortex, Hypothalamus, brainstem
- Visible behavior
Try to connect each of the steps of the emotional circuitry to a specific disorder - i.e. which area tends to be targetted?
- Detection of environmental stimuli
- senses, thalamus
- reduction of impulses -> Autism, Stress, ADHD
- Quick interpretation
- hippocampus, amygdala
- reduction of overactivity -> anxiety, PTSD
- Evaluation of these signals
- Prefrontal cortex, Nucleus accumbens
- restoring cognitive control -> anxiety, PTSD, ADHD, addiction
- Action Preparation
- Motor cortex, Hypothalamus, brainstem
- restore automatic nerve system - PTSD
- Visible behavior
How do we treat ADHD? Which area does it target? What is meant by self-medication
- Activation, primarily, prefrontal cortex
- Medication:
- Ritalin - lowers impulsivity, nordrenergic
- Prozac - depression, s&d&d
- Adderall - dopaminergic
- Self-medication:
- smoking, nicotine (activates acetylcholine receptors)
What do - Prozac, Ritalin, Aderall - have in common?
They are all reuptake inhibitors i.e. they block the reuptake making dopamine, serotonin, and norepinephrin available for longer and in greater quantities
- But remember it has widespread effect -> some side effects may arise
Small note: what are the neurotransmitter systems that extend to the prefrontal cortex and from where?
- Dopamine - ventral tegmental area
- Serotonin - Raphe nuclei
- Norepinephrin - Locus coeruleus
- Acetylcholine - Basal Forebrain
- Histamine - Tubero mammilaris
What neurotransmitter is synthesized here? What structures are we looking at?
What is the staining substance?
Dopamine - VTA and substantia nigra - tyrosine hydroxylase
What are the 2 main functions of the dopaminergic neurons (names of the pathways)? What drugs affect it?
- Nigro-striatal (SN) - modulates cortical motor control and action selection
- Meso-cortical/limbic (VTA) - reward processing, motivation, modulation of cognitive (executive) control
Recall: What is retrograde tracer? How can we target more than just the primary connection cells?
= tracing technique which follows proteins from the terminal buttons back to the soma of the cell
- If we want to extend its effect - we need to put the tracer into a virus -> if we wait long enough we could infect/spread to the whole brain
What kind of projections does VTA make ?
- Nucleus accumbens
- Medial shell
- GABA and dopamine
- Lateral shell
- Core
- dopamine
- Medial shell
- Prefrontal cortex
- Prelimbic area
- Infralimbic area
- Basolateral amygdala
Do you remember the research with rat and reward self-administration?
A rat was given opportunity for intracranial self stimulation via Medial forebrain bundle every time she pushed a lever => these rats prefered such stimulation over food, drinks => died of exhaustion
Can we have something like this in humans? What would be the targets?
Yes. Deep brain stimulation
- treatment for Parkinson’s
- treatment for resistant depression (especially anhedonia = inability to feel pleasure)
- targets: thalamus, internal capsule, cingulate gyrus, medial forebrain bundle
What are the following structures?
- Substantia nigra
- Medial forebrain bundle
- Caudate-putamen
- Nucleus accumbens
- Olfactory tubercle
- Hippocampus
- Olfactory tract
There was one more research into stimulating rat’s medial forebrain bundle - what was it all about?
They injected an electrode to specific columns for rat whiskers and another to the medial forebrain bundle -> by stimulating the whiskers they could signal to the rat to turn left/right -> if she did so she would be rewarded by the boost in MFB
- Research wanted to explore options for survaillence of buildings affected by an earthquike
What is the relationship of dopamine and working memory? How did they research that?
Research: rats were put into 8-arm radial maze in which only 4 doors were open to exploration and contained some food -> after collecting the food there was a delay -> rat put back, this time the other doors were open
- ideally rat should go to the unexplored doors
If they were high ot low on DA => more erros
=> Inverted U shape
How does dopamine correlate with PFC firing?
If there is only dopamine release (without any other stimulation) -> no change in spontaneous activity of PFC
BUT if DA and hippocampus activate -> Inverted U shape
What kind of relationship do we expect with Ritalin? What may influence that?
Look at what area is affected in Parkinson’s:
What do we use as a model for Parkinson’s?
Alfa-synuclein transgenic mice -> genetically modeled in a way so that alfa-synuclein accumulates -> SN cell death ->disturbed motor pattern, distance and speed deficiencies
Where is noradrenaline synthesized? Where does it have its projects? What is the main function? What drug affects it?
Synthesis = locus coeruleus, projections = all over the brain, function = arousal and stress response, drug = amphetamine
Look at how locus coeruleus looks like in a real brain:
Explain the steps of biosynthetic pathway for catecholamine neurotransmitters:
What does the supply of NE facilitate in the following structures - Basolateral amygdala, Centra nucleus of amygdala Dentate gyrus, medial PFC,
Just like dopamine, noradrenaline is also all about the firing frequency - what functions does it influence?
How did they demonstrate the involvement of locus coeruleus in cognitive flexibility?
Research: rat was taught to lick its whiskers -> if it licked the right = reward, left = nothing -> then the rule was switched
Results:
=> those that were faster at switching showed higher activity in locus coeruleus
=> if LC stimalated, switch became even faster
What increases NE availability?
Explain working memory task shown in the picture:
Research: monkeys fixated on a point -> multiple cues appeared in a sequence -> delay -> the monkey had to perform saccades in the same order and direction
-> they recorded one neuron
Results:
=> Neurons seemed to encode the info in working memory with regard to their spatial tuning
How was this tuning affected by adding or removing NE?
In both cases -> firing lost its specificity and the brain wouldn’t know where exactly the cue occured
What is the synthesis process of serotonine?
From where and to where does serotonine project? What processes does it affect?
- synthesis = Raphe nuclei (dorsal and medial)
- projections = all over cortex
- Involved in:
- gut mobility and vascular system
- mood, appetite, circadian rhythm, arousal, migranes, pain
Look at Raphe nuclei in a rats brain:
+ what is the staining substance?
Staining: 5-hydroxy tryptamine
What was found in a study on depressive relapse (therapy x medication)?
The most effective approach in treating mood disorders is to combine cognitive therapy with medication (instead of relying on one or the other)
- They both target the same regions of interest
