Cell Bio 2 Exam 2 L23: Neural Plasticity 2

1. Induction: a postsynaptic neuron realizes that a particular input needs to be changed

2. Selectivity: a particular type of change is selected based upon input parameters

3. Expression: The synaptic efficacy is changed

4. Maintenance: This efficacy is maintained over a long period of time

Modulation is when synaptic efficacy is changed (time scale of minutes to hours)

• Types: 
• -biochemical: modulation of receptors
• -stoichiometric: adjustment of PSD components
• -structural: spine morphology

• the conductive properties of receptors
• ligand gating

• -remember CaMKII
• -increase conductivity

-ERKII mediated (similar to CamKII)

• -decrease conductivity
•         -K+ is concentrated inside the cell
•         -K+ channel opening allows repolarization (because K+ leaves)
•         -recovery of resting potential

stoichiometry: relative amount of reactants to products; i.e. amount of receptor to signaling proteins at the PSD (think of the PSD as a tiny reaction chamber)

• AMPAR is "louder" than NMDAR
• -easier to excite
• -stays open longer

• NMDAR is activated first
• -calcium influx affects the PSD-95 binding

• AMPAR is recruited for potentiation
• -other proteins bind PSD-95
• -AMPAR is recruited to the PSD

• extrasynaptic locations
• -spine membrane versus the presynaptic terminal 
• -diffusion and neurotransmitter uptake
• -synaptic vesicle release

• little effect at extrasynaptic locations
• PSD-95 mediates recruitment
• synaptic AMPAR increases synaptic efficacy

• Spine morphology changes
• -intitially: "stubby" spine
• -potentiated: "mushroom" spine

• What are the effects?
• -the spine "neck" constricts (dendrite access)
• -resistance to ionic movement = (1/cross sectional area)
• -ohms law: V = IR; increase R = increased V, shrinking neck increases R therefore increases V
• -increasing V helps reach threshold for action potential

1. Molecular switches: the state of a molecule / complex is maintained

2. bistable feedback of signaling cascades: signaling cascade turns "on"/"off" with large perturbations 

3. Membrane trafficking: if located in the membrane, it will keep replenishing

4. Local protein synthesis: "tagged" spines get more protein synthesized

5. Recurrent network dynamics: cycling signals keep connections strong

molecular activation can occur via phosphorylation or protein binding into complexes

• maintenance of phosporylation state:
• -phosphorylation activates proteins
• -some proteins can phosphorylate themselves
• -CaMKII activation allows autophosphorylation

• Maintenance of protein binding complexes:
• -when partners bind, they may activate/inactive
• -calcium/calmodulin binds CaMKII and activates it
•        -once bound, this complex can be very stable
•        -activated CaMKII is more likely to bind calmodulin (higher affinity)

A signaling network is a series of coupled proteins; a signal travels from one protein to the next and activity "jumps" between proteins in the pathway.

• ERKII/PKC pathway: 
• -small activations of ERKII die out along the pathway
• -large activations of ERKII are perpetuated and result in a positive feedback loop
• -activated ERKII activates PKC and phosporylates K+ channels
• -positive feedback loop maintains ERKII activation and maintains K+ channel phosphorylation

• stoichiometry changes during facilitation/depression
• -cellular machinery can replace old proteins with new
• -if the protein is already in the PSD, the machinery replaces it there

• Back to the NMDAR/AMPAR relationship
• -facilitation is caused by some excitatory signals
•          * NMDAR mediates the initial event
•          * AMPAR increases in abundance at the PSD
•          * AMPAR is stabilized there
• -cellular machinery
•          * normally replenishes AMPAR (and others)
•          * When AMPAR is not at the PSD there is no reason for the machines to insert it
•          * When AMPAR is abundant at the PSD the machinery inserts it there to replace the old

• Flow of information
• -DNA-->RNA-->protein

• Translational regulation
• -synthesis
•        *activation states of proteins can affect mRNA binding and translation
• -accesibility
•        * if the mRNA is not around, it cannot be translated to protein
• -"tagged"synapses
•        * events may cause biochemical changes at the synapse; these changes can affect local protein synthesis
•        * the type of regulation depends on plasticity; LTP may result in increased protein synthesis but LTD may result in degradation of those mRNA molecules
•        * regulation also depends on the protein; LTP may increase synthesis of certain proteins (AMPAR) and degrade others (K+ channels)

• Neuronal communication can be:
• -point to point: info passed to different regions of the system
• -resonant: activity can bounce back and forth between two regions
• -cyclic: activity can circle within a region or around multiple regions

• The pre-frontal cortex and short-term memory:
• -pre-frontal cortex (PFC) is associated with learning and memory
• -cognitive tasks activate the PFC
• -learning tasks cause the activity to continue
•        *continued cycling is afforded by attention
•        *this denotes importance (non-attentive stimuli will die out)
•        *reinforced stimuli are brought into long term memory
• -intraregional cyclic recurrent network activity