Blood-Brain Barrier and Neurotransmission

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Questions and Answers

If a novel neurotoxin selectively disrupts the function of astrocytes surrounding cerebral blood vessels, leading to a compromised blood-brain barrier, which of the following consequences would be MOST likely?

Enhanced paracellular permeability to hydrophilic substances and ions, disrupting neuronal excitability. (correct)
Increased transcytosis of large peptides due to endothelial cell hyperpolarization.
Selective apoptosis of neurons expressing NMDA receptors due to glutamate excitotoxicity.
Upregulation of P-glycoprotein efflux transporters, actively removing lipophilic drugs from the brain.

In the context of Parkinson's disease treatment, what is the MOST critical pharmacokinetic advantage of L-DOPA over dopamine itself that allows it to effectively reach the brain?

L-DOPA's reduced molecular weight allows for enhanced passive diffusion across endothelial cell membranes.
L-DOPA is resistant to enzymatic degradation by catechol-O-methyltransferase (COMT) in the periphery.
L-DOPA exhibits significantly higher binding affinity to dopamine receptors, requiring lower dosage.
L-DOPA is a substrate for the large neutral amino acid transporter (LAT1) at the BBB, facilitating its entry. (correct)

Considering the mechanisms of psychoactive drugs, if a compound increases the concentration of a neurotransmitter in the synaptic cleft by competitively inhibiting the enzyme responsible for its degradation, it would be classified as a(n):

Agonist, that enhances the action of the neurotransmitter.
Indirect antagonist, reducing downstream receptor activation through allosteric modulation.
Indirect agonist, potentiating neurotransmitter activity via an alternative mechanism. (correct)
Receptor desensitizer, leading to compensatory downregulation of postsynaptic receptors.

If a novel drug is found to selectively enhance GABA's affinity for its receptor without directly activating the receptor itself, this drug would MOST accurately be classified as a(n):

Allosteric GABA modulator, potentiating GABAergic transmission without direct receptor activation. (D) Signup and view all the answers

Given alcohol's dual effects on glutamate and GABA neurotransmission, what neural mechanism BEST explains the anterograde amnesia often associated with acute alcohol intoxication?

Disruption of synaptic plasticity in the hippocampus due to combined glutamatergic antagonism and GABAergic agonism. (B) Signup and view all the answers

If a research study reveals that chronic alcohol exposure leads to a compensatory downregulation of GABA receptors and an upregulation of glutamate receptors in the central nervous system, this adaptation is MOST likely to manifest as:

Increased susceptibility to seizures during alcohol withdrawal due to reduced inhibitory tone. (B) Signup and view all the answers

Considering the synergistic effects of Rohypnol and alcohol, what is the MOST critical mechanism underlying the increased risk of respiratory depression and overdose when these substances are co-administered?

Additive potentiation of GABA-A receptor activity, causing supramaximal inhibitory effects on respiratory centers. (B) Signup and view all the answers

In the context of neurotransmitter termination within the synaptic cleft, what distinguishes enzymatic deactivation from reuptake with respect to their mechanisms of action?

Enzymatic deactivation entails the degradation of neurotransmitters via enzymatic activity; reuptake involves the active transport of intact neurotransmitters back into the presynaptic neuron. (D) Signup and view all the answers

Acetylcholinesterase (AChE) inhibitors are sometimes used therapeutically. Considering the mechanism by which AChE operates, what would be the immediate consequence of administering an AChE inhibitor?

Prolonged presence of acetylcholine (ACh) in the synaptic cleft, leading to increased postsynaptic receptor activation. (C) Signup and view all the answers

Consider a scenario where a novel synthetic compound is introduced into a neuronal synapse. Electrophysiological recordings reveal an immediate increase in postsynaptic neuron excitability, yet subsequent analysis indicates no direct interaction of the compound with the postsynaptic receptors themselves. Which presynaptic mechanism could plausibly account for these observations?

The compound selectively blocks presynaptic voltage-gated potassium channels, prolonging action potential duration and enhancing neurotransmitter release. (D) Signup and view all the answers

A researcher is investigating a novel neurotransmitter receptor subtype. Initial data suggests that upon activation, this receptor initiates a signaling cascade that ultimately leads to decreased expression of a specific gene in the postsynaptic neuron. Which type of receptor is MOST likely involved in mediating this effect?

A G-protein coupled receptor (GPCR) that modulates gene transcription via second messengers. (B) Signup and view all the answers

A newly developed drug selectively targets and impairs the function of glial cells within the central nervous system. What specific impact might this drug have on synaptic transmission?

Reduced neurotransmitter reuptake and clearance from the synaptic cleft. (D) Signup and view all the answers

Within the context of metabotropic receptor signaling, how does the activation of phospholipase C (PLC) contribute to intracellular signaling diversity?

PLC cleaves PIP2 into IP3 and DAG; IP3 releases calcium from intracellular stores, while DAG activates protein kinase C. (B) Signup and view all the answers

A patient presents with symptoms suggestive of a neurodegenerative disorder characterized by progressive motor dysfunction and cognitive decline. Imaging studies reveal significant atrophy of the basal ganglia and cerebral cortex. Pharmacological investigations indicate a marked reduction in the concentration of a specific neurotransmitter within these brain regions. Furthermore, genetic analysis identifies a mutation in a gene encoding an enzyme critical for the synthesis of this neurotransmitter. Which neurotransmitter system is MOST likely implicated in this disorder?

The dopaminergic system, with a mutation in tyrosine hydroxylase. (B) Signup and view all the answers

A researcher discovers a novel compound that readily crosses the blood-brain barrier (BBB) and selectively enhances the activity of a specific population of inhibitory interneurons within the cerebral cortex. Paradoxically, electrophysiological recordings reveal a net increase in the overall excitability of cortical pyramidal neurons following administration of this compound. Which mechanism best explains this seemingly contradictory observation?

The compound selectively inhibits a distinct population of other inhibitory interneurons (disinhibition), resulting in a net increase in pyramidal neuron activity. (B) Signup and view all the answers

Given a scenario where a patient presents with symptoms indicative of increased intracranial pressure, but a lumbar puncture is contraindicated due to suspicion of a posterior fossa mass, which alternative diagnostic procedure would provide the MOST clinically relevant information regarding the patient's CSF dynamics and potential obstructive hydrocephalus?

Radionuclide cisternography to visualize CSF flow pathways and identify potential blockages or abnormal absorption. (D) Signup and view all the answers

Following a traumatic brain injury, a patient exhibits signs of chronic traumatic encephalopathy (CTE). The initial injury caused a cascade of cellular events. Which of the following molecular mechanisms is MOST directly implicated in the neurodegenerative progression characteristic of CTE?

Aberrant hyperphosphorylation of tau protein leading to the formation of neurofibrillary tangles and disruption of axonal transport. (B) Signup and view all the answers

In the context of neuronal electrophysiology, assume a neuron is at rest. Which modification to the ionic environment would MOST selectively diminish the amplitude of an Excitatory Postsynaptic Potential (EPSP) without substantially altering the Resting Membrane Potential (RMP)?

Applying a competitive antagonist to postsynaptic glutamate receptors, effectively reducing the number of activated receptors. (C) Signup and view all the answers

Considering the intricate interplay of meningeal layers and cerebrospinal fluid (CSF) dynamics, which of the following scenarios would MOST directly lead to communicating hydrocephalus?

Impairment of CSF absorption at the arachnoid granulations due to fibrosis or obstruction following subarachnoid hemorrhage. (D) Signup and view all the answers

Under conditions of significant neuronal depolarization, if voltage-gated $Mg^{2+}$ channels in NMDA receptors are persistently blocked, what is the MOST immediate consequence regarding synaptic plasticity?

Attenuation of long-term potentiation (LTP) due to reduced $Ca^{2+}$ influx. (A) Signup and view all the answers

In a complex neural circuit, a researcher introduces a selective agonist for presynaptic $GABA_B$ receptors on glutamatergic neurons. What is the MOST probable downstream effect of this manipulation?

Reduced release of glutamate due to decreased $Ca^{2+}$ influx into the presynaptic terminal. (B) Signup and view all the answers

Imagine that researchers have developed a novel neuroprotective agent that selectively enhances the efficiency of CSF turnover. Which of the following mechanisms would MOST likely account for its therapeutic effect in the context of traumatic brain injury (TBI)?

Enhanced clearance of excitotoxic neurotransmitters and metabolic waste products from the extracellular space. (A) Signup and view all the answers

In the context of action potential propagation, a neurotoxin selectively blocks voltage-gated potassium channels in a myelinated axon. What is the MOST immediate consequence of this blockade on the characteristics of the action potential?

Prolongation of the repolarization phase and increased duration of the action potential. (C) Signup and view all the answers

Given the intricate interplay between GABAergic interneurons and dopaminergic neurons in the context of reward circuitry, and considering the established actions of opioids, which of the following scenarios would MOST efficiently amplify dopamine release in the nucleus accumbens?

Introducing a viral vector expressing Cre-dependent inhibitory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) in VTA GABAergic neurons, coupled with systemic administration of CNO (clozapine-N-oxide) at a precisely titrated dose. (A) Signup and view all the answers

In the context of cocaine's mechanism of action within the mesolimbic dopamine system, what would be the MOST direct consequence of administering a vesicular monoamine transporter 2 (VMAT2) inhibitor following chronic cocaine exposure?

Attenuated dopamine release into the synapse due to impaired vesicular storage, potentially leading to a reduction in cocaine-seeking behavior. (D) Signup and view all the answers

Considering the neuroanatomical organization of the central nervous system (CNS), specifically the arrangement of meningeal layers and their relationship to brain vasculature, which of the following statements accurately describes the functional significance of this architecture?

The pia mater, being highly vascularized, directly regulates blood flow to specific cortical regions based on local neuronal activity, thereby optimizing metabolic support and waste removal. (A) Signup and view all the answers

Given the anatomical directions within the nervous system, if a researcher states they are making a coronal cut, what are they describing?

A cut that separates the front of the brain from the back of the brain. (B) Signup and view all the answers

A novel neurotoxin selectively targets and ablates cells within the ventromedial hypothalamus (VMH). Considering the established functions of the VMH, which of the following behavioral and physiological changes would be MOST anticipated in an affected organism?

Significant impairments in female-typical sexual behavior, alongside potential metabolic dysregulation and increased susceptibility to diet-induced obesity. (A) Signup and view all the answers

In the context of neural communication within the peripheral nervous system (PNS), if a researcher discovers a novel compound that selectively disrupts the structural integrity of the nerve sheath, what would be the MOST likely consequence on axonal function?

Reduced fidelity of signal transmission, leading to action potential failure and impaired coordination of motor and sensory functions. (A) Signup and view all the answers

Given the actions of heroin, and the naturally occurring 'reward' system, what is the MOST likely mechanism by which heroin creates the sensation of euphoria?

Heroin binds to opiate receptors, decreasing GABA release. Because GABA typically inhibits dopamine release, dopamine is then able to be released without the inhibitory effect from GABA. (B) Signup and view all the answers

Damage to which of these areas would MOST directly impair executive function, as measured by performance on the Wisconsin Card Sorting Test?

The dorsolateral prefrontal cortex, due to its role in working memory and cognitive flexibility. (C) Signup and view all the answers

Flashcards

Presynaptic Events

Events occurring before neurotransmitter release into the synaptic cleft.

Postsynaptic Events

Events that occur after neurotransmitter binding at the postsynaptic receptor.