exam 3 study guide (AI-based flashcards)
The three major classes of neurotransmitters (Amino Acids, Amines and Peptides)
ACh
The properties of ACh synthesis, vesicle packaging (VAChT), degradation and choline reuptake
The importance of Acetylcholinesterase (AChE)- role in ACh breakdown in the cleft.
Know what Sarin gas poisoning does to the AChE role
Structure, function and pharmacology of ACh receptors: both ionotropic at skeletal muscles (made up of 5 subunits, receptor activated by 2ACh molecules, has an intrinsic ion channel that is a non-selective cation channel)
And metabotropic muscarinic receptors in heart pacemaker cells (ACh released from vagus nerve slows down heart rate by activation a heteromeric G protein (Galphai) that reduces Ca2+ influx and increases K+ efflux, to slow rising phase of the action potential
Cause and treatment of Myasthenia Gravis (autoimmune disease leading to loss of skeletal muscle ACh receptors), and electrophysiological findings from EMGs and biopsies
GABA and Glycine
The properties of GABA (GAD) synthesis, vesicle packaging (VIAAT) and reuptake (GAT)
The structure, function and pharmacology of GABA/Glycine ionotropic receptors (5 subunits, intrinsic Cl selective channel)
The types and roles of Chloride transporters in establishing Cl reversal potential in immature and mature neurons and how this relates to excitability- rule of thumb…if the Cl reversal potential is above the firing threshold (as in immature neurons) GABA will cause action potentials…so at this stage GABA is excitatory). In mature GABA synapses, the Cl- reversal potential is below firing threshold so GABA release would be inhibitory (ie move membrane potential closer to Cl- reversal potential)
The pharmacology of GABA (benzodiazepines enhance GABA receptor activation, picrotoxin inhibits GABA receptors) and Glycine receptors (strychnine inhibits Glycine receptors)
Cause of Familial startle disease-hyperekplexia due to glycine receptor mutation
Actions of Baclofen on GABAB receptors
Biogenic amine transmitters
What are the catecholamines (DA, NE and E)?
What common precursors (Tyrosine) and metabolic machinery do they have in common? How are they packaged into vesicles (VMAT), re-uptake (DA-DAT, NE/E NET) degraded (COMT MAO)?
The other two biogenic amines are serotonin (5HT) and histamine
What cognitive processes are they involved in?
What happens in Parkinson’s Disease (DA neuron death) and how can this condition be treated ? (L-DOPA, MAO and COMT inhibitors, Deep-Brain Stimulation, ultrasonic ablation)
What does MPTP do to cause Parkinson’s-like symptoms (loss of DA neurons in Substantia Nigra due to free radical production)
How do Nor/Epinephrine (speed up due to Beta receptor activation of Galphas activation resulting in more Ca2+ influx and decreased K+ efflux) and ACh (slows heart rate) affect heart rate?
What does Reserpine do and what medical conditions has it been found helpful for?
What are the 3 major classes of drugs used to treat depression and how do they act?
-serotonin re-upake inhibitors (SERTs eg Prozac), MAO and COMT inhibitors
Peptides
How are prepropeptides generated and targeted to the ER lumen? Role of the signal sequence, SRP, translocon and peptidase.
Where and how does substance P act in the pain pathway (C-fiber release onto dorsal horn ascending neurons) and how do endogenous opioids regulate pain perception (produce analgesia by inhibiting C-fiber release of substance P)
Which animals do not respond to capsaicin
Understand the role of ATP as a co-transmitter (packaged into vesicles by VNUT, acts on purine receptors)
Understand how unconventional transmitters (endocannabinoids - anandamide or 2-AG- synthesized from membrane phospholipids and NO synthesized by Ca-CAM activation of NOSynthase) rely on Ca2+ for synthesis, but are not released from synaptic vesicles as they are membrane permeant.
GPCRs
What is the difference between autocrine, paracrine and endocrine signaling?
What happens when a ligand binds to a GPCR? Role of GAPs and GEFs
What is the difference between a heteromeric G-protein (α, βγ) and a monomeric G protein (Ras, Rab Rho etc)?
Which steps following GPCR activation produce an amplification of signaling?
What are the different sources of Ca2+ that can lead to increased cytoplasmic Ca2+ (plasma membrane channels and some receptors, ER IP3 and ryanodine receptors) and its subsequent removal (plasma membrane Ca2+ pump, Na+/Ca2+ exchanger, mitochondrial and ER uptake, calbindin)
What is the relationship between Ca2+, calmodulin (4 Ca2+ bind to one calmodulin which can activate CamKinases by acting on regulatory domains?
What protein is critical for the worm defecation cycle and what does it do (IP3 receptor?
What enzyme produces cAMP (adenylate cyclase)?
What targets of cAMP do you know of and how do they act (PKA and cAMP-gated channels? What role does cAMP play in olfaction (depolarization through cAMP-gated channels) ?
Short term synaptic plasticity
The different forms of short term synaptic plasticity (Facilitation, depression, augmentation, potentiation) and underlying causes
Conditions that produce habituation (repeat siphon stimulation) and sensitization (tail shock) of the Aplysia Gill Withdrawal Reflex
Know which synapse is enhanced during sensitization in the gill withdrawal reflex (siphon sensory neuron) and what the release of serotonin(5-HT) onto this synapse does (increased release through S type K+ channel inhibition).
What is the source of serotonin responsible for sensitization of the gill withdrawal reflex (facilitatory interneurons)?
5HT stimulates a G-protein coupled pathway to bring about sensitization. You should know the signaling pathway (GalphaS, adenylate cyclase activation, increased cAMP, PKA activation, phosphorylation of K+ channels) and how this increases neurotransmitter release. Understand the experimental data supporting this 5HT pathway.
Invertebrate Synaptic Plasticity
Review the genes implicated in fly olfactory learning
Review Aplysia Long-term sensitization…activation of CREB-1(CRE activation) and removal of CREB-2 (transcriptional repressor) signaling and downstream functions of ubiquitin hydrolase
Glutamate transmission
How is glutamate synthesized (glutaminase), packaged into vesicles (VGLUT), and removed from the synaptic cleft (EAATs)?
What are the 3 classes of ionotropic glutamate receptors (AMPA, Kainate, NMDA).
What are the structural and functional specifics of AMPA and NMDA receptors?
AMPA fast component of EPSP, Na/K permeability, single channel biophysics resulting from tetramers with 4 glutamate binding sites
NMDA slower component of EPSP, Na/K/ Ca2+ permeant, glycine co-factor, Mg2+ block giving rise to voltage-sensitivity….understand the current voltage-relationship of NMDA responses with and without glycine and Mg2+
Be prepared to address the roles of NMDA and AMPA receptors in CA3-CA1 LTP.
Why are NMDA receptors coincidence detectors?
What are two causes of glutamate excitotoxicity
What happens during ischemia? Lack of O2, reduced ATP, loss of ATP-dependent pumps, increased glutamate signaling, excessive depolarization, increased Ca2+ signaling, apoptosis