Neuroscience exam 4 study set

What are the 3 hallmarks of ADHD?

Impulsivity, inattention, & hyperactivity.

What statements describe the functions of DA & NE in relation to ADHD?

Low to moderate levels of D1 receptor stimulation are optimal for PFC function.

High levels of norepinephrine (NE) release exclusive stimulate a2A receptors

Modest levels of NE release are beneficial for PFC function by stimulating a2A receptors.

Phasic DA firing is associated with reward, reinforcement and motivation

Baseline DA & NE firing is fast & tonic

High levels of NE release impair working memory by recruiting a1 & b1 receptors.

Low to moderate lvls of D1 receptor stimulation are optimal for PFC functions.

Modest lvls of NE release are beneficial for PFC by stimulating a2A receptors.

Phasic DA firing is associated w/ reward, reinforcement & motivation.

High levels of NE release impair working memory by recruiting a1 & B1 receptors.

What is the hypothetical effect of augmenting a stimulant with a2A agonist in ADHD patient with oppositional symptoms?

Optimizes NE levels, enhancing the signal and improving behavior.

What is a potential advantage of using slow-release stimulant formulation to treat ADHD?

Reduced risk of abuse due to more gradual increase in DA levels.

What is the role of synaptic pruning in cognitive development during childhood?

Removes overproduced/weak synapses, allowing cognitive intelligence to mature.

What is the theoretical outcome of concurrent stimulation of a2A and D1 receptors in the PFC?

Increased signal & reduced noise, leading to improved attention, focus, & emotional control.

What is the role of the VMAT in DA regulation?

Transports DA into vesicles preventing toxic levels in the neuron & synapse.

What are the correct descriptions of the roles & effects of a2A & D1 receptors in the cortical pyramidal neurons in the PFC?

cAMP links a2A and D1 receptors to hyperpolarization-activated cyclic nucleotide-gated HCN cation channels

DA & NE binding at their respective receptors has the same effect on cAMP

DA binding to D1 receptors has an excitatory effect on cAMP

Open HCN channels cause incoming signals to leak out before they can be transmitted.
a2A & D1 receptors are located on dendritic spines of cortical pyramidal neurons in the PFC allowing them to gate incoming signals

Closed HCN channels prevent incoming signals from the bain passed along

NE binding to a2A receptors has an inhibitory effect on cAMP

cAMP links a2A & d1 receptors to hyperpolarization-activated cyclic nucleotide-gated HCN cation channels

DA binding to D1 receptors has an excitatory effect on cAMP

a2A & d1 receptors are located on dendritic spines of cortical pyramidal neurons in the PFC, allowing them to gate incoming signals

NE binding to a2A receptors has an inhibitory effect of cAMP.

Which symptom of ADHD is linked to DLPFC?

Sustained attention.

Why is low to moderate DA stimulation important to PFC functioning in ADHD patients?

Optimized PFC functioning by stimulating D3 & D1 receptors appropriately.

What is tonic firing with phasic bursting?

Tonic firing keeps circuit to default.

Phasic firing temporarily increases activity; thereby reinforces synaptic connection

Too much phasic firing in reward circuits can induce uncontrolled DA firing

How can uncontrolled DA firing from phasic firing be induced? What are the outcomes?

Can be induced by too much phasic firing; drugs of abuse

Reward circuits are hijacked & impulses are followed by development of uncontrolled compulsion of drugs.

What is synaptic weight?

Mathematical representation of impact of a presynaptic neuron on a postsynaptic neuron.

Not fixed; adjust based on activity patterns; LTP & LTD

What factors determine synaptic weighing?

Amount of neurotransmitter released

Receptor sensitivity

Number of receptors

What is there to know about synaptic pruning & ADHD?

Altered synaptic pruning during critical periods of brain development may contribute to ADHD.

Either insufficient or excessive pruning may disrupt neural circuit balance.

What is a potential long-term consequence of drug-induced Da release in the mesolimbic pathway?

Neuroadaptation leading to migration from ventral striatal loop to dorsal striatal loop, causing a cycle of addiction, dependence & withdrawal.

What is the role of the hypothalamus in regulating appetite & which peptides are primarily involved in appetite stimulation & suppression?

Uses neuropeptide Y, agouti-related peptides to stimulate appetite while POMC neurons produce a-MSH which suppresses appetite via MC4 receptors.

What is the mechanism of action of nicotinic partial agonists (NPAs) in nicotinic cholinergic receptor activity?

NPAs stabilize nicotinic receptors in an intermediate state.

What are the parts of the mesolimbic DA pathway?

NA & VTA.

What is the description of impulsive & compulsive brain circuits?

Impulsivity: Ventral striatum, T, VMPFC, & ACC

Compulsivity: Dorsal striatum, T & OFC

Which of the statements about marijuana & cannabinoid receptors are correct?

Active ingredient in marijuana is THC

Interacts w/ CB1 receptors to trigger DA release from the mesolimbic reward system.

Which similarities exist between impulsive-compulsive disorders & drug addiction?

Both diminish pleasure/gratification over time despite repetitive engagement

Both involve DA dysregulation in the mesolimbic pathway

Both involve arousal/tension in anticipation of the behavior & drug use

Both require increasing ‘doses’ to achieve the same effects over time akin to tolerance.

What are the functions of Da in the mesolimbic pathway?

Facilitating natural highs from activities like achievements or enjoying meals

Regulation or reinforcement and reward.

What is tolerance?

After repeated administration a given dose of a drug produces a decreased effect or when increasingly larger doses must be administered to obtain the effects observed with the original use.

What is dependence?

Physiological state of adaptation produced by repeated administration of certain drugs when they are abruptly discontinued and have withdrawal effects distinct from motivational changes.

What is addiction?

Behavioral pattern of drug abuse characterized by overwhelming involvement of a drug (compulsive use) the secure of its supply & a high tendency to relapse after discontinuation.

What is cross tolerance & crossdependence?

Ability of a drug to suppress the manifestation of physical dependence produced by another drug & maintain the physically dependent state.

What are the characteristics of impulsivity in the context of drug use?

Initial impulse to take a drug leads to great pleasure & satisfaction

Impulsivity shifts to compulsivity as ventral circuits give way to dorsal circuits.

True or false: endocannabinoids are primarily retrograde transmitters.

True.

What is the primary mechanism of action for naloxone & naltrexone in the treatment of opioid overdose?

They act as opioid receptor antagonists, competing w/ opioids at their receptor sites to reverse their effects.

What is there to know about the effects of 1 pack of cigarettes?

Its enough to keep all nicotinic receptors desensitized for a day.

What is nystagmus?

A condition of rapid involuntary & uncontrolled eye movements.

What are the stages and ongoing processes of Alzheimer’s?

Stage 1: amyloidosis

Stage 2: amyloidosis with neurodegeneration

Stage 3: amyloidosis, neurodegeneration and cognitive decline

Which of the following best describes the hypothesized role of glutamate in Alzheimer’s disease?

 AMPA receptors block NMDA receptor activity during excitatory neurotransmission

Amyloid plaques and tangles reduce glutamate release, preventing neurotransmission.

Excessive glutamate release may lead to excitotoxic cell death in neurons.

Excess glutamate release improves synaptic transmission and enhances memory.

Glutamate has no effect on memory or learning in Alzheimer’s disease.

Excessive glutamate release may lead to excitotoxic cell death in neurons.

What factors increase the likelihood of progression from MCI to Alzheimer’s dementia?

The presence of the E4 genotype.

What condition must occur simultaneous for NMDA receptor activation during excitatory neurotransmission?

Glutamate binding, glycine binding and neuronal depolarization.

Which is hypothesized to contribute to the link between type 2 diabetes and Alzheimer’s dementia?

Decreased insulin concentration and insulin receptors in the brain.

Which is accurate regarding amyloid pathology in Alzheimer’s disease?

Amyloid pathology can occur in the presymptomatic stage of Alzheimer’s disease.

Which are the diagnostic criteria for cognitive or behavioral impairment?

Primarily identified through patient history and cognitive assessment

Not explained by delirium or major psychiatric disorder

Represent a decline from previous levels of functioning and performing

Interfere with the ability to function at work or usual activities.

Which of the following correctly describes the role of α-secretase in APP processing?

α-Secretase cleaves APP to form amyloidogenic peptides.

α-Secretase is inhibited in the non-toxic pathway of APP processing.

α-Secretase cleaves APP close to the membrane, producing non-toxic peptides.

α-Secretase directly generates the toxic β-amyloid peptides.

α-Secretase functions exclusively within the nucleus of the neuron.

a-Secretase cleaves APP close to the membrane, producing non-toxic peptides.

Which is true regarding the progression of MCI to dementia?

Approximately half of amyloid-positive MCI patients progress to dementia within a year.

Which cognitive domains are evaluated to detect impairment in patients with possible dementia?

Language functions

Visuospatial ability

Personality, behavior, or comportment changes

Reasoning and handling of complex tasks

Ability to acquire and remember new information.

What is there to know about Muscarinic acetylcholine receptors in relation to dementia?

They are G-protein linked

Muscarinic 1 (M1) receptors are involved in the regulation of memory.

What is there to know about Nicotinic receptors in relation to dementia?

They are ligand-gated w/ 2 important types

a7: presynaptically facilitate excitation; postsynaptically help regulate cognitive function

a4B2: regulate DA release in NA.

What is there to know about Encephalitis lethargica & the LDOPA experiments?

Cause of EL is unknown; characterized by delayed physical/mental response & lethargy.

LDOPA experiments restored physical & cognitive functioning.

LDOPA experiments provide strong evidence that neurotransmitters enable consciousness.

Why do the LDOPA experiments provide strong evidence of enabling consciousness?

Patients showed reduced physical/mental responses.

Post treatment patients could not recall catatonic state; ‘awoke’ after LDOPA treatments.

What is there to know about Amyloid Plaques and Neurofibrillary tangles in relation to Dementia?

Amyloid plaques are clumps of beta-amyloid protein fragments that disrupt cell communication. These plaques can develop years before cognitive impairment symptoms appear.

Neurofibrillary tangles are tau protein fibers inside neurons, which tangle, disrupting the transport of signals. Over time, this leads to cell death & brain atrophy.

What is the amyloid cascade hypothesis of dementia?

Suggests amyloid buildup initiates a cascade that leads to neurofibrillary tangles and neurodegeneration.