Local and Genomic Protein Synthesis in Long-Term Potentiation

Vocabulary flashcards covering the molecular mechanisms of local dendritic translation, genomic signaling cascades, BDNF/TrkB/mTOR pathways, and protein degradation in synaptic plasticity and LTP consolidation.

De Novo Protein Synthesis Hypothesis (DNPS)

The hypothesis proposing that the establishment of long-lasting synaptic changes and the consolidation of long-term potentiation (LTP) require the creation of new proteins.

Plasticity Products

New mRNAs and proteins generated following the activation and phosphorylation of transcription factors in the nucleus that modify synapses to sustain long-lasting LTP.

Synapse-to-Nucleus Signaling

A genomic signaling cascade wherein stimulation of a postsynaptic neuron activates second messengers that stimulate protein kinases, which then translocate to the nucleus to phosphorylate CREB protein.

Soma-to-Nucleus Signaling

A signaling route where action potentials produced by LTP induction open voltage-dependent calcium channels (vdCCs) on the somatic membrane, causing calcium influx that signals CREB phosphorylation within and outside the nucleus.

Two Waves of Protein Synthesis

The sequential model for LTP maintenance consisting of an initial wave occurring locally in the dendrites from existing mRNAs, followed by a second wave translated from new mRNAs generated by the genomic cascade.

Dendritically Localized mRNAs

Transcripts distributed within the dendritic arbor near spines that can be locally translated, specifically including mRNAs that encode AMPA receptors and CaMKII.

Protein on Demand

An efficient and flexible system where pre-transported dendritic mRNAs are stored in compartments near dendritic spines and translated locally only when stimulated by synaptic activity.

RNA-Binding Proteins (RNA-BPs)

Proteins that recognize and bind specific sequence elements within mRNAs, attaching them to cytoskeleton motor proteins such as kinesin and dynein for microtubule transport.

5' TOP mRNAs

mRNAs containing $5'$ terminal oligopyrimidine tracts that code for regulatory translation machinery, including initiation factors (IFs) and elongation factors (EFs).

mTOR (Mammalian Target of Rapamycin)

A complex protein kinase activated downstream of TrkB receptor stimulation that promotes translation by blocking the inhibitory influence of the repressor protein 4E-BP.

4E-BP

An inhibitory translation factor that represses the translation of TOP mRNAs until it is inactivated by mTOR signaling.

Functional Polyribosomal Complex

A fully assembled translational unit formed when small ribosomal (SR) subunits combine with initiation factors (IFs), elongation factors (EFs), and mRNAs to synthesize proteins locally at active spines.

TrkB Receptor

The neurotrophin receptor for BDNF colocalized with NMDA and AMPA receptors, whose activation is required to trigger local dendritic translation via the mTOR pathway.

TrkB Time Window for Local Synthesis

The temporal limit of local translation requirement demonstrated by pharmacological inhibition: blocking TrkB at $0\,\text{min}$ abolishes enduring LTP, whereas inhibition at $80\,\text{min}$ has no effect, showing local protein synthesis takes less than $80\,\text{minutes}$.

Ubiquitin-Proteasome System (UPS)

A dendritic protein degradation system activated by glutamate transmission that facilitates plasticity and memory consolidation by degrading existing proteins that regulate or suppress translation.

CaMKII in UPS Recruitment

A protein kinase that plays a critical role in recruiting proteasome complexes to dendritic spines following synaptic stimulation.