week 1 Flashcards
levels of research
- basic: fundamental questions about how neurons work
- translational: testing hypothesis about disease and potential therapies in the most appropriate animal models
- clinical: testing potential therapies in humans
6 electrical properties of neurons
- have negative membrane potentials (voltages) at rest
- Vrest is usually around -70mV but varies across cell types
- generate AP to transmit electrical signals (not all neurons make APs tho)
- APs an all of nothing event and always the same size
- Vrest and AP are controlled by the activity of ion channels in the cell membrane
- Ion channels come in many forms (diff combos of ion channels lead to diff signaling patterns in diff types of neurons)
the Nernst equation
simplified Nernst equation
Goldman-Hodgkin-Katz (GHK) equation
Feedback Cycles:
- responsible for membrane potential changes during an AP
- POSITIVE feedback loops create the AP
- Na+ channel inactivation terminates the AP
- later, large K+ currents return cell to Vrest
- hyperpolarization removes inactivation from Na+ channels preparing neuron for next AP
2 types of refractory periods and how they work:
ABSOLUTE REFRACTORY PERIOD
- time window after AP where no amount of stimulation can evoke another AP
1. inactivation of Na+ channels
2. slow deactivation of K+ channels (large outward current acting to hyperpolarize cell)
RELATIVE REFRACTORY PERIOD
- time window where another AP can be initiated with sufficiently large depolarization input currents
- amt required to override residual K+ current slowly decreases back to normal threshold as the K+ deactivates
- imposes a limit of how many AP/sec a neuron can produce (rate limit is about 1000 APs/sec)
What are the main differences between electrical and chemical synapses?
Electrical:
- faster, inflexible, and more short term
- support synchronized firing of neurons in network
- common in invertebrates bc great for predetermined bx in short-lived organisms
- CANNOT support learning
Chemical:
- slower, more flexible, and longer effects
- REQUIRED for learning
- iontotropic or metabotropic
2 types of neurotransmitter receptors
2 types of post synaptic potentials
Excitatory Post Synaptic Potentials (EPSPs)
- goal is to convert chemical signal to graded electrical potential that may or may not cause an AP in the receiving neuron
Inhibitory Post Synaptic Potentials (IPSPs)
- when a NT causes a HYPERpolarization
Inhibitory Post Synaptic Potentials (IPSPs):
- usually rely on ionotropic chloride ion channels
- when open they slightly hyperpolarize the membrane but mainly make it very difficult for a neuron to be excited by other inputs (suppress or prevent neural activity)
- GABA and Glycine are the most common inhibitory NTs (act on ionotropic Cl- ion channels in the post-synaptic membrane)
Integration (summation)
- most neurons integrate many inputs from both excitatory and inhibitory synapses onto their dendrites
2 types of neurotransmitters
small molecule transmitters
large molecule peptide transmitters
small molecule transmitters:
- amino acid transmitters: Glutamate, GABA, Glycine
a. two types of ionotropic glutamate receptors (AMPA- and NDMA- type) plus 3 groups of metabotropic glutamate receptors (mGluR 1-8)
b. GABA(a) and Glycine are ionotropic and GABA(b) is metabotropic - Acetocholine (nAChR-ionotropic and mAChR-metabotropic)
- Biogenic amines: Norepinephrine (NE), 5-HT(seratonin), Dopamine (DA), Histamine
- mostly metabotropic; broad actions throughout brain that influence arousal and motivation - ATP: the purines (purinergic) synapses:
- two types P(2x) ionotropic and P(2Y) metabotropic - Gases: Nitric Oxide (NO) and Carbon Monoxide (MO)
- Endocannabinoids: 2-AG and anandamide
Large molecule Peptide Transmitters:
- short amino acid sequences
- all metabotropic
- > 60 amino acids or longer
- ex: substance P, orexin, opioids, oxytocin, vasopressin
Structure of nicotinic Acetocholine receptors (nAChR)
- ligand-gated ion channel is compromised of 5 individually transcribed protein units
- channel is assembled in the membrane from subunits
- a-subunit contains the extracellular binding site for ACh
Ionotropic GABA receptors:
- GABA(A) receptor
- same design as nAChR (5 subunits)
- binding sites for many clinically important molecules
