Neurobio EXAM 2

What is the role of the VTA?

With reward system; reward prediction error signal.

the larger the magnitude of the reward….

The more you will work for it

Which neurotransmitter reflects reward behavior?

Dopamine “pleasure”

Which system causes a state of pleasure?

u-opiod system

What happens to dopamine levels in the brain when you abuse substances?

A rise especially in nucleus accumbens

If you take psychostimulants, what will occur

A pseudo-activation of your sympathetic nervous system

Cocaine

blocks monoamine uptake mechanisms (more in cleft)

Amphatemines

Reverses monoamine uptake mechanisms

Monoamines types:

Epinephrine, norepinephrine, dopamine, and serotonin

Serotonin, norepinephrine, dopamine. Organize what dopamine will uptake in ORDER and then also norepenephrine

1.3.2

2>3>1

Classic amphetamine/methams

Strongly act on dopamine transporters and norepinephrine transporters. Release in striatum and nucelus accumbens. Rewarding/euphoric feeling

D-amphetamine (adderall)

Prefrontal cortex. dopamine transporter expression is low, norepinephrine effects dominate. Alert and thinking. Releases both dopamine and norepinephrine

MDMA (Ectasy)

Strong norep and serotonin expression. Stimulant and different than meth

Dopamine system

Cocaine blocks, amphetamine reverses

projections with drugs (simplified)

VTA to CP and nucleus accumbens to FC

If there is a lesion in the mesocorticolimbic pathway what occurs?

Prevents stimulating effects of drugs

If you block the dopamine receptors in the VTA

There will be a decrease of reward behaviors but not all due to habit and amygdala connection (learning associations that are hard to break)

Opoids

Drugs originally derived from the poppy plant

Which receptors are activated with opiods?

GABAergic receptors in the VTA- provide inhibition of VTA dopamine neurons

Activation of opioid receptors

Disinhibits dopamine neurons, increasing activity of dopamine neurons and increasing release of dopamine

Opioid types

Morphine, heroin, fentanyl

what happens if you block receptors in the nucleus accumbens?

Reduces power of opioids but not always criticical for heroin self-administration. But area is still reinforcing

Ultraradian

Less than a day, breathing

Circadian

~24 hour cycles (sleep, waking)

Infradian

Many days; human reproductive cycle

Circannual

Once a year; migration or mating

Zeitgeber

Light training on circadian rhythm

Endogenous rhythm

Circadian rhythms are generated internally, even without external cues, but can be synchronized with the environment

SCN suprachiasmatic nucleus

Located in the hypothalamus, has specialized retinal ganglion cells with melanopsin —> coordinates hormonal and automatic outputs to get self ready

SCN pt.2

2. uses neural routes to influence other hypothalamic nucleus that regulates many different systems/behaviors

Research with fruit flies

Short lives, don’t need a lot of space in lab, small genome = great for studying genes

Drosophila clock PER

Circadian oscillation of mRNA and potein levels —> mutations influence time clock duration

Early part of the day=

CLOCK and CYCLE —> activates transcription of PER and TIM 

In the night

protein degredation —> Cryptochrome (CRY) responds to blue light and synchronizes the clock with the cycle—> degrades protein —> cycle starts again

form a dimer at night…

Shut down their own transcription and degrades

Behavioral definition of sleep

Reduced motor activity, decreased response to stimulation, stereotypic postures,reversability

What stage of sleep do you start out when you first start?

nREM

Dolphin sleep

Unihepispheric slow-wave sleep (USWS). one hemisphere of the brain sleeps at a time. Allows for constant surfacing of air

Function of sleep

Conserve energy, thermoregulation, avoid predators, restore body, consolidate memories

NREM sleep promoting areas

1. ventrolateral preoptic area (VLPO)

2. Anterior hypothalamus

3. Basal forebrain

REM sleep promoting areas

Pons pontine reticular formation

Wake promoting areas

Hypothalamus: histaminergic neurons, hypocretin/orexin system

Ascending cholinergic; serotonergic and noadrenergic systems

Amygdala

Diffuse arousal network

Norepinephrine, serotonin, histamine, acetylcholine

Orexin

Promotes wakefulness and inhibits REM sleep (excites systems)
If knocked out = narcolepsy

Which brain region is most directly associated with reward-prediction error signaling?

Ventra Tegmental Area

Which neurotransmitter system is most critical for the reinforcing effects of psychostimulants like cocaine and amphetamines?

Dopamine

How does cocaine primarily affect monoamine signaling?

Blocks monoamine reuptake

How do amphetamines differ from cocaine in mechanism of action?

They reverse dopamine transporters and drive release

Which amphetamine is most associated with strong serotonin release, contributing to empathogenic effects?

MDMA

Which brain pathway is essential for psychostimulants’ locomotor-stimulating effects?

Mesocorticolimbic pathway

What is the classic mechanism for opioid reinforcement in the VTA?

Disinhibition of dopamine neurons via GABA inhibition

Which receptor type mediates most euphoric effects of opioids?

u-(mu)-opioid receptor

What structure is the master circadian clock in mammals?

SCN

Which hormone’s release is strongly regulated by the SCN through the pineal gland?

Melatonin

Which photopigment in the retinal ganglion cell help synchronize circadian rhythms to light?

Melanopsin

In fruit flies, which gene was the first clock gene identified?

Per

What EEG pattern is seen during wakefulness?

Beta waves

Which is known as paradoxical sleep?

REM sleep

Which system is crucial for wakefulness and attention?

Diffuse arousal network

Loss of hypocretin (orexin) neurons is associated with which sleep disorder?

Narcolepsy

Which factor most directly signals homeostatic sleep pressure?

adenosine accumulation

Emotional state

Stress, anxiety, and emotional arousal can interfere with sleep onset, while relazation techniques help promote relaxation conducive to sleep

Cognitive factors

Racing thoughts or worrying can inhibit sleep onset, but mindfulness and cognitive techniques can help quiet the mind

Fatal familial insomnia (FFI)

Inherited prion disease that affects the brains sleep and autonomic systems. Mid adulthood, vivid dreams and difficulty falling asleep. Fatal. Hallmark is insomnia

Diseases that impair memory

Alzheimer’s, Korsakoff’s

Lashley Experiments

-Made lesions of different sizes in cortex

-Lesions affected the number of errors made (memory problem) 

-No correlation to performance with any particular brain region

Patient HM

No formation of new memories. Remembers everything before but not after (anterograde amnesia)

-Star mirror drawing task-improves even though no rememberance

Declaritive memory

Facts and events

Non-Declaritive memory

Procedural, skeletal musculature, emotional responses (last two are classical conditioning)

Semantic Memory

FActs and lists. Takes effort. Knowledge learned over many interactions

Episodic Memory

Memory for specific events that you have experienced - just happened, no effort

Toman Experiment

Investigated how rats form cognitive maps to navigate complex mazes. Flexible maps!

Hippocampal place cells

Fires when an animal occupies a specific location within its environment. Crucial for understanding spatial cognition and mmemory. Recorded using calcium imaging techniques

Grid cells

Provide information about space:

-Position determined by center

-Distance determined by the distance between center and adjacent 

-Angular information from center and adjacent

Morris Water maze

Rats with hippocampal damage take longer to find the hidden platfom compared to control animals. Inefficient search strategies and fail to learn spatial location

Radial arm maze

Multiple rooms from one platform -studies versatility, etc…

Why study L&M in Aplysia?

-Simple nervous system

-20,000 cells

-Large, identifiabl neurons and axons

-Simple behaviors can be modified by learning

Gill withdrawal reflex

Habituation to siphon that would originally squirt water :(

Level of acetylcholine during REM

HIGH

Triggers of onset of sleep

Circadian, homeostatic sleep drive (adenosine accumulation), environment, behavior, temperature, cytokine production (when sick)

If you have narcolepsy, you should take

Provogil

Which autonomic functions arise with fatal familial insomnia?

Hypertension, tachycardia, hyperhidrosis

Lashley’s maze: problems

The lesions will make so many impairments that make the experiment hard to reproduce and do. Many different pathways, motor impairments, etc…

Phenotypes of Sham rage

Undirected aggression

Phenotypes of Kluver-Bucy Syndrome

Loss of fear, hyperorality, hypersexuality, visual agnosia, hypermetamorphosis (distracted), dietary change

with sapolsky, what happened during the drought of 1984?

Less food = higher cortisol = more aggression

When is vasopressin activated?

elevated when drops in osmalarity or blood pressure

Pre synaptic

More ca2+ means more release of neurotransmitters, bigger PSP

Post-synaptic

More receptors, means bigger PSP

PKA- Aplysia

Activation increases cAMP which phosphorylates and closes voltage-dependent S type K+ channels -→ greater calcium influx

PKC- Aplysia

Activated via the DAG/IP3 pathway and reduces a resting (leak) K+ channel

-Also phosphorylates components of the release machinery to boost exocytosis efficiency

What morphological changes are associated with long-term sensitization?

Long-term changes by repetitive serotonin release associated with growth

What produces long-term memory in Aplysia?

Repeated stimulation leads to an accumulation of kinases. translocate to the nucelus, activate CREB, translation of new proteins, protein inhibitors block long-term memory

Synaptic consolidation

Long term memory requires transcription and translation of new proteins

Three main areas of the hippocampus

Dentate gyrus, Ca1, Ca3

Ca1 pathway

Ca1 → subiculum → (fornix) → entorhinal cortex

Trisynaptic pathway

Perforant pathway to dentate gyrus -→ mossy fibers to Ca3 → Schaffer collaterals to CA1

Temporoammonic (direct) pathway

Direct projects from EC superficial layers CA1 and subiculum

Role of dentate gyrus in memory

Pattern seperation, Distinguishes between similar experiences or contexts