Calculate the impact on cellular activity if a G_s protein is constitutively active, assuming it directly stimulates Adenylyl Cyclase .

Constitutive activation of $G_s$ leads to continuous production of cAMP from ATP , resulting in sustained overactivation of PKA and potential over-phosphorylation of downstream targets like CREB , leading to persistent changes in gene expression.

Differentiate the signal amplification potential between an ionotropic receptor and a metabotropic receptor .

Ionotropic: Low amplification; binding directly opens an ion channel with a 1:1 or limited stoichiometry. Metabotropic: Very high amplification; one receptor activates multiple G-proteins , each activating effector enzymes that generate thousands of second messenger molecules.

Predict the effect on intracellular $Ca^{2+}$ concentration following the activation of a $G_q/11$-coupled receptor .

Activation of $G_q/11$ stimulates Phospholipase C (PLC) to hydrolyze PIP_2 into IP_3 and DAG . The IP_3 diffuses to the endoplasmic reticulum and binds to $IP_3$-gated channels, triggering the release of stored $Ca^{2+}$ into the cytoplasm.

Explain the role of the glutamate–glutamine cycle in maintaining synaptic connectivity via astrocytes .

Astrocytes uptake synaptically released glutamate to prevent excitotoxicity and convert it into glutamine via glutamine synthetase . This glutamine is then transported back to the presynaptic neuron to be recycled into glutamate, ensuring the continuous availability of the neurotransmitter for future signaling.

Describe the mechanistic step of G-protein activation mediated by a GPCR acting as a GEF .

When an agonist binds, the GPCR induces a conformational change in the associated heterotrimeric G-protein , causing the $\alpha$-subunit to release GDP and bind GTP , triggering the dissociation of the $\alpha$-GTP complex from the $\beta\gamma$-complex .

Calculate the effect on cGMP levels if nNOS is inhibited during NMDA receptor-mediated retrograde signaling.

Inhibition of nNOS prevents the conversion of L-arginine and $O_2$ into Nitric Oxide (NO) . Without NO as a gaseous messenger to activate the soluble guanylyl cyclase (sGC) in the target cell, cGMP levels will fail to increase, blocking the retrograde adjustment of presynaptic strength.

Identify the primary function of PKA in coupling transient extracellular signals to long-term structural changes .

PKA phosphorylates transcription factors like CREB , which translocate to the nucleus and bind to CRE (cAMP Response Elements) on DNA, initiating the transcription of genes required for synaptogenesis and sustained modifications of synaptic morphology.

Determine how spine morphology (e.g., mushroom vs. stubby ) influences the probability of functional interaction between synapses.

Mushroom spines generally represent mature, stable synapses with large postsynaptic densities. Stubby spines facilitate more direct, less spatially constrained signaling. Greater spine density and spatial proximity of these diverse shapes increase the likelihood of functional connectivity and integration within neural circuits.

Explain the bi-directional control of Adenylyl Cyclase (AC) by G_s and G_i proteins.

AC acts as a molecular coincidence detector: G_s -coupled receptors stimulate its enzymatic activity to increase cAMP production, while G_i -coupled receptors inhibit AC , thereby reducing cAMP levels and dampening the signaling output.

Contrast the two mechanisms of Tyrosine Kinase-Linked Receptor (TRK) activation.

Intrinsic catalytic domain: The receptor itself possesses kinase activity that autophosphorylates upon ligand binding (e.g., Trk receptors for neurotrophins). Associated intracellular kinases: The receptor lacks intrinsic activity and relies on recruiting and activating non-receptor kinases like JAKs (e.g., cytokine receptors).

List the four fundamental steps in a molecular signaling cascade .

The four steps are: 1. Release of a first messenger ; 2. Detection by a specific receptor ; 3. Activation of a transduction system (second messengers/scaffold proteins); 4. Activation of a target molecule (ion channel, enzyme, or transcription factor).

Calculate the result of GTPase activity in the $\\alpha$-subunit of a G-protein .

The intrinsic GTPase activity hydrolyzes bound GTP back to GDP . This hydrolysis causes the $\alpha$-subunit to re-associate with the $\beta\gamma$-complex , thereby terminating the signaling cascade initiated by the GPCR.

Explain the significance of RAREs (Retinoic Acid Response Elements) in nuclear receptor signaling .

RAREs are specific DNA sequences in the promoter regions of target genes. Retinoic acid-activated RAR/RXR heterodimers bind to these elements to recruit transcriptional machinery, directly regulating the expression of genes essential for synaptogenesis and structural plasticity.

Predict the consequence of blocking protein phosphatases in a cell with ongoing PKA-mediated phosphorylation .

Blocking phosphatases removes the regulatory 'off' mechanism that counteracts kinase activity. This leads to a runaway accumulation of phosphorylated target proteins , artificially extending the duration of the signal and potentially causing dysregulation of synaptic plasticity.

Describe the functional role of the second messenger $Ca^{2+}$ in the PLC/PKC pathway .

Following IP_3 -mediated release from the ER, $Ca^{2+}$ acts as a critical cofactor that binds to PKC , facilitating its translocation to the plasma membrane and its subsequent activation, which then leads to phosphorylation of proteins involved in neurotransmitter release and gene regulation.

Molecular Mechanisms Of Neuronal Signal Transduction And Synaptic Plasticity Flashcards

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Molecular Mechanisms of Neuronal Signal Transduction and Synaptic Plasticity

This deck covers the molecular cascades, receptor classes, and biochemical pathways essential for understanding neural communication and synaptic adaptation.

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by @esme_hodari

Q: Calculate the impact on cellular activity if a G_s protein is constitutively active...

Q: Differentiate the signal amplification potential between an ionotropic rece...

Q: Predict the effect on intracellular $Ca^{2+}$ concentration following the activatio...

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