Neurobiology Exam 2

Spatial summation

 PSPs arriving on different dendritic sites at the same time; the summation at the axon hillock of postsynaptic potentials from across the cell body; if this summation reaches threshold, an action potential is triggered

Temporal summation

PSPs arriving at different times from the same synapse; the summation of postsynaptic potentials that reach the axon hillock at different times; the closer in time the potentials occur, the more complete the summation

Small frequency stimulation

localized calcium increase near small vesicle fusion events

High frequency stimulation

large, terminal-wide calcium increase mobilization of dense-core vesicles

Ionotropic receptors

kind of receptor (ligand-gated ion channel; fast): neurotransmitter binds to receptor → ions immediately flow

Metabotropic receptor

kind of receptor (G-protein coupled receptor; slow): neurotransmitter binds to receptor → activate G proteins, moves to ion channel

Patch clamping

 allows for isolation of individual ion channels; a very tight contact between the pipette and membrane is created so ions cannot flow through particular ion channels.

Researches manipulate the voltage across the membrane or whole cell and measure the resulting ionic currents; they can also control the current and measure the voltage changes

Whole-cell recording

patch clamp recording that record current from whole cell membrane

Inside out recording

patch clamp recording where cytoplasmic side is exposed to external media; best for studying influence of intracellular molecules on ion function

Outside-out recording

patch clamp recording where external side is exposed to bath which isolates channel; best for studying how channel activity is affected by external molecules

Na+ currents

• The channels open/activate in response to depolarization

• The onset of activation is variable: not always an immediate response to depolarizing current; they remain activated for a variable period of time

• The channels inactivate relatively quickly

• Inactivated state transition to closed state is voltage dependent

K+ currents

__Current via patch clamp:

No inactivation: current flows for the entire duration of depolarization

Delayed rectifier

type of K+ channel where delay between depolarization and opening of K+; flow as long as membrane channel is depolarized

type A channel

type of K+ channel where open with depolarization but K+ flow quickly stops

Herg channel

type of K+ channel that is opened by hyperpolarization; mediates the repolarizing K current of the action potential: current flows after depolarization ends

inward rectifier

type of K+ channel that activates in response to hyperpolarization; helps establish resing membrane potential during the undershoot

Calcium-activated gK+

type of K+ channel that contributes to the afterpotential and regulate cell excitability; lower calcium concentration shifts the K+ conductance and membrane potential

Two-pore channel

type of K+ channel where unique 2-pore structure gated by pH

Reuptake

the process by which released synaptic transmitter molecules are taken up and reused by the presynaptic neuron, thus stopping synaptic activity

(Type of way neurotransmitter is removed)

Degradation 

the chemical breakdown of neurotransmitter into inactive metabolite

(Type of way neurotransmitter is removed)

Autoreceptors

 a receptor for a neurotransmitter located in the presynaptic membrane which signals how much transmitter has been released

(Type of way neurotransmitter is removed)

Acetylcholine synthesis

Choline Acetyl-transferase synthesizes acetylcholine → it is loaded into small, clear vesicles → acetylcholine is release and binds to ligand gated channels in muscle fibers→ Na+ carries the depolarizing current at the neuromuscular junction (acetylcholine is the neurotransmitter being released) → out of the cell it is degraded by acetylcholinesterase 

Glutamate synthesis

Glutamine and glutaminase create glutamate → glutamate binds to the receptor → Na+ channel opens → depolarization = EPSP ; EATT glutamate is then converted back into glutamine

GABA recycling

GABA and glycine receptors in the CNS are transmitter-gated Cl- channels: GABA binds to receptor→ Cl- channel opens → hyperpolarization = IPSP (reduces the membrane potential) 

reuptake by glia cells → converted to glutamine → uptake by neuron or direct uptake by neuron

Paracrine signaling

 chemical communication that involves the secretion of chemical signals onto a group of nearby target cells

Endocrine signaling

chemical communication that involves the secretion of hormones into bloodstream where they affect targets throughout the body

Cell signaling molecules (aka, First messengers)

cascade is initiated when this binds to a cell-surface receptor and initiates intracellular activity; this is an extracellular substance (such as a neurotransmitter) or a hormone

receptors

specialized protein molecules that detect and respond to chemical or physical stimuli by initiating a cellular response.

G-proteins

has alpha, beta, and gamma subunits which interact together and with the receptor

Alpha subunit binds to GDP/GTP

Beta gamma subunit always work together

Alpha or beta gamma can be the effector

effector proteins

a protein that modulates the activity of another protein or biological process

second messengers

Molecules that relay signals from receptors on cell surface to target molecules inside the cell and amplify affect of first messenger and target kinases and phosphotases; they include calcium, cAMP, and inositol triphosphate, they are NOT proteins.

later effectors

 immune cells or signaling molecules that act in a delayed response during an immune reaction

transcription factors

proteins that bind to specific DNA sequences to control the rate of gene transcription, acting as molecular switches that turn genes on or off.

cell impermeant

these are signaling molecules that cannot permeate membrane of neuron and typically bind to receptors associated with cell membranes; these are short-lived and rapidly metabolized, internalized by endocytosis

cell permeant

these are signaling molecules that can cross the plasma membrane to act directly on receptors that are inside the cell; they are relatively insoluble in aqueous solutions and transported in blood where they can persist for hours or days

cell associated

 signaling molecules that are arrayed on the extracellular surface on the plasma membrane; they act only on other cells that are in physical contact with the cell that carries the signal

Calcium

Second Messenger: 

Sources: Extracellular (fluid): NMDR, rdCC, intracellular (endoplasmic reticulum): RyR, Ip3R

Targets: Calmodulin, and protein kinase C (PKC)

Cyclic AMP

Second Messenger:

Sources: Synthesized from ATP by adenylyl cyclase, often activated by G-proteins.

Targets: protein kinase A (PKA), which phosphorylates other proteins.

Cyclic GMP

Second Messenger:

Sources: Synthesized from GTP by guanylyl cyclase. 

Targets: protein kinase G (PKG) and ion channels

IP3

Second Messenger:

Sources: Generated from the breakdown of PIP2 by phospholipase C (PLC). 

Targets: the IP3 receptor, a channel on the endoplasmic reticulum that releases Ca2+

Diaglycerol

Second Messenger: 

Sources: Generated from the breakdown of PIP2 by phospholipase C (PLC). 

Targets: It recruits and activates protein kinase C (PKC) to the plasma membrane.

Heterotrimeric

G-protein coupled receptor where G-protein activation involves a three-subunit alpha, beta, gamma, protein complex that dissociates upon activation

an external stimulus to a GPCR causes the alpha subunit to exchange GDP for GTP, which then dissociates from the beta gamma dimer, and both activated subunits can then signal downstream. 

monomeric

G-protein coupled receptor where G-proteins are single-subunit proteins that do not form such complexes and signal through different effector pathways. 

G-proteins, like Ras, are activated directly at the membrane via a similar GDP/GTP exchange mechanism but signal to effectors that are not associated with GPCRs. 

synpatic plasticity

The ability of synapses to strengthen or weaken over time in response to changes in activity

Ca2+

The mechanism underlying synaptic facilitation:

Rapid increase in synaptic strength due to prolonged elevation of ______ in the presynapse. 

synaptic depression

The mechanism underlying ________________:

A decrease in synaptic strength due to sustained synaptic activity (tetanus) caused by progressive depletion of pool of synaptic vesicles ready for release

facilitation

synaptic change that lasts for hundreds of milliseconds

depression

synaptic change that lasts from hundreds of milliseconds to tens of seconds.

augmentation

synaptic change that lasts for several seconds, typically longer than facilitation but shorter than post-tetanic potentiation

post-tetanic potentiation

synaptic change that persists for several minutes after the train of stimuli has ended. In some cases, it can last for tens of minutes.

LTP

A strong stimulus potentiated (modified) the synapses to produce a more robust response

NMDA

Induction but not expression of LTP depends on ______ receptors

• Glutamate must bind to _____ receptors to induce LTP and strengthen synapse but does not need to bind for continued expression

• The ______ receptor binds glutamate. It also binds Mg2+ because Mg2+ binds to the NMDA channel

AMPA

Induction and expression of LTP depends on ________receptors

• Influx of Ca2+ via NMDA receptors activate Ca2+ calmodulin dependent protein kinase (CaMKII) which leads to:

  • 1. New ______ receptors inserted into post-synaptic membrane

  • Modification of existing _____ receptors which allows for more Na+ influx since the channel stays open longer

• Constant things typing to remove _____ receptors to return it to its unpotentiated state

LTD

a process that weakens synaptic connections between neurons, the opposite of long-term potentiation (LTP). It is experimentally induced by prolonged, low-frequency stimulation (e.g., 1 Hz for 5–15 minutes) of the synapse, which leads to a decrease in the efficacy of synaptic transmission

Specificity of LTP

Coordinated activity of the presynaptic and postsynaptic neuron strengthens the synapse

• If the pre synaptic activities are synchronized with post synaptic activities the synapse will be strengthened
  

BCM Theory

There is a sliding threshold for LTP or LTD induction on which is stabilized by an adaptation of time-averaged postsynaptic activity

• When a presynaptic neuron fires LTP will be produced at a synapse if the post-synaptic neuron is in a highly active state

• LTD will be produced at a synapse of the postsynaptic cell is in a low activity state

• Presynaptic activity followed by post-synaptic action potential = LTP

• Postsynaptic action potential precedes presynaptic activity = LTD

Spike Timing Dependent Plasticity

Precise timing of presynaptic and postsynaptic activity determines the polarity (LTP vs. LTP) of long lasting synaptic plasticity

• Pre must occur before post (about 40 milliseconds) for LTP

Sensory transduction

the process by which sensory receptors convert physical or chemical stimuli into electrical signals that the nervous system can interpret.

tonotopy

High frequency sounds have the greatest effect near the base where the basilar membrane is narrow and relatively thick

Low frequency sounds produce larger responses near the apex where the basilar membrane is wider and more flexible