Synaptic Communication Flashcards
4 benefits of electrical signaling
- covers long distances with minimal loss of signal
- rapid
- quickly repeated
- information can be conveyed in patterns
4 limitations of electrical signaling
- binary
- difficult to modify
- energy intensive
- microenvironment dependent
What is the resting membrane potential?
- the potential energy in the electrical gradient formed across the plasma membrane
- caused by formation of K+ concentration gradient and permeability of the membrane to K+
- K+ concentration high inside cell, low outside cell; Na+ opposite
- K+ moves out of cell down concentration gradient, and is then pulled back into the cell via the electrical gradient: causes internal membrane to be negative and external membrane to be positive
Ohm’s Law
V = IR
V is the voltage (plasma membrane)
I is the current
R is the resistance (ion channels)
Electrochemical equilibrium
- When the concentration and electrical gradients for an ion are in balance
- driven by diffusion of ions
Na+/K+ ATPase
- important ion transporter
- establishes Na+ and K+ gradients across the neuron membrane
- actively moves Na+ and K+ against concentration gradient
Ion channels
- passive proteins
- allow ions to diffuse down concentration gradient
- K+, Na+, Ca2+, and Cl- channels
Neuron membrane at rest
- interior of neuron is negatively charged
- separation and slow flow of K+ ions across plasma membrane creates membrane potential
- Na+/K+ ATPase activity maintains electrochemical gradients
- membrane potential allows neuron electrical activity
What two equations calculate membrane potentials?
- Nernst equation - equilibrium potential of an individual ion
- Goldman equation - equilibrium potential of the entire plasma membrane
Neuron passive electrical state
- cytoplasm is electrically resistant
- neurons electrically inert
- passive current rapidly decays over space and time
- active current flow allows neuron electrical information transfer
Passive current flow
- current decays
- cytoplasm resistance
- relative to distance
Active current flow
- current repropogates
- active process
- relative to distance
The action potential
- rapid change in membrane potential
- caused by sequential opening of Na+ and K+ channels
- requires Na+ and K+ gradients
4 types of ion channels
- leakage - constant ion flow along gradient
- voltage-gated - respond to changes in membrane potential
- ligand-gated - respond to ligand binding; NT, proteins, ions, & lipids
- physically-gated - respond to other physical stimuli; mechanical, temperature, light
4 types of transporters
- ATPase pumps - use ATP to move one or more substrates
- ion exchangers - energy from moving one+ ions along concentration gradient will move other ions against gradient; opposite directions
- co-transporters - one+ ions move another ion; same direction
- multiple transporter systems - multiple transporters working together to move substrate
Voltage-gated ion channels
- physical conformation changes with membrane polarization
- time and charge dependent
- ions move along concentration gradients
- passive
- refractory period
Ligand-gated ion channels
- ligand binds, changes conformation of channel to allow ion movement along concentration gradient
- diversity of ligands
- passive
- open in presence of sufficient ligand and appropriate environment state
Na+/K+ ATPase pumps
- bind Na+ on inside of cell
- phosphorylated, changing structure of transporter to open to exterior
- Na+ released, K+ binds
- causes dephosphorylation of transporter, allowing K+ inside
Is the neurons resting potential positive or negative?
- negative
- in an AP, membrane potential is stimulated, rapidly goes positive, and then returns to the negative state
Name the 6 phases of APs
- resting phase
- activation phase
- rising phase
- falling phase
- undershoot phase
- recovery phase
What occurs during the resting phase of an AP?
- very little activity
- slow leakage of K+ out of cell through k+ channel from
What occurs during the activation phase of an AP?
-stimulus is induced, opening Na+ channels
What occurs during the rising phase of an AP?
- voltage-gated Na+ channels open, causing a dramatic and rapid influx of Na+ ions
- charge of membrane is reversed (+ in, - out)
- voltage-gated K+ channels open
What occurs during the falling phase of an AP?
- voltage-gated Na+ channels close
- voltage-gated K+ channels open, K+ moves out
- leaves a more negative state on the inside of the cell
What happens during the undershoot phase of an AP?
- refractory period prevents voltage-gated Na+ channels from opening
- no AP can occur
- voltage-gated K+ channels close
What happens during the recovery phase of an AP?
-leaky K+ channels re-establish the resting potential
What part of the neuron is an AP initiated?
axon hillock
What direction is an AP conducted?
- anterograde; away from cell body
- unidirectional
Two ways to increase AP conductance
1) increase axon caliber
- reduces internal resistance; energy intensive; physically restrictive (squid example)
2) insulate axons (myelination)
- prevents current leakage, requires glial support, oligodendrocytes (CNS), Schwann cells (PNS)
- saltatory conduction
2 major classes of neurotransmitters
small molecules and neuropeptides
small molecule NTs
- amino acids or derivatives
- synthesized in presynaptic terminal
- stored in small synaptic vesicles
- released from the presynaptic terminal
- examples are glutamate, GABA, & Acetylcholine
neuropeptide NTs
- proteins
- synthesized in the body
- stored in large vesicles
- released both pre- and postsynaptically, and into extracellular environment
- Ex. brain gut peptides, opioid peptides, etc.
Synaptic transmission steps (8)
- AP
- Ca2+ channel depolarization
- Ca2+ influx
- synaptic vesicle fusion
- NT release
- NT receptor activation
- NT reuptake
- NT sequestration/metabolism
3 distinct pools for synaptic vesicles
- readily releasable pool
- recycling pool
- reserve pool; tethered to actin and can be released
- these are important in stages of release
SNARE complexes
- proteins that allow vesicle release
- include synaptobrevin, syntaxin, SNAP-25, and synaptotagmin
Steps in NT release
- vesicle docks
- SNARE complexes form to pull membranes together
- entering Ca2+ binds to synaptotagmin
- Ca2+-bound synaptotagmin catalyzes membrane fusion by binding to SNAREs and the plasma membrane
2 models of membrane reuptake and vesicle reformation
- classic synaptic vesicle cycle
- ultrafast synaptic vesicle cycle (more likely/ faster)
2 NT receptor types
- ionotropic
- metabotropic
Ionotropic NT receptors
- ligand binding opens ion channel
- variable selectivity for ions
- not necessarily uni-directional
- directly involved in creating postsynaptic electrical current and changing membrane potential
- excitatory (depolarizing) or inhibitory (hyperpolarizing)
Metabotropic NT receptors
- G-protein coupled intracellular signals
- relatively slow activation time
- prolonged signal duration
- signals modify the activity of ionotropic receptors, ion channels, and transporters
- signals alter terminal structure and function
Change in post-synaptic membrane potential by NT receptors
- Excitatory postsynaptic potential (EPSP) - depolarization; Na+, Ca2+
- Inhibitory postsynaptic potential (IPSP) - hyperpolarization; Cl-, K+
Influence of location on synaptic input strength
- membrane potentials decay with space and time
- proximity to the trigger zone dictates the relative influence of a synaptic input
Postsynaptic potential summation
- the total change in membrane potential based on the spatial (location) and temporal (frequency) aggregation of postsynaptic potentials
- sufficient depolarization triggers an AP
- think about inhibitory and excitatory signals
Where are emotional and abstract states mapped in the brain?
deep brain areas
Where are maps overlaid and compared?
association cotrices
What are spinal reflexes?
Sensory and motor loops that function independent of descending brain control. Example is hitting the patellar ligament with a mallet and the result is a leg kick.
What is the Hebbian Theory?
Neuronal networks undergo activity-dependent plasticity throughout life, and activity drives neural network consolidation, while inactivity leads to decay.
You are born with many more neuron than you end up with as an adult. How is this related to the Hebbian Theory?
Synapse pruning (loss of synapses) occurs during development as a result of the strengthening of some synapses and the subsequent loss of others.
Name the 6 changes at synaptic terminals that drive neuronal plasticity
1) increased/decreased synaptic vesicle release
2) increase/decreased receptor density
3) changes in receptor sensitivity and conductance
4) changes in receptor subtype expression
5) sprouting of new synapses
6) formation of new connections
How do networks change as a result of Long-term Potentiation (LTP) and Long-term Depression (LTD)?
Strength of connections and number of connections can change
Explain the somatosensory circuit of touch
Three neurons communicate peripheral sensation to the brain:
1st order: mechanosensory neuron –> brainstem (medulla)
2nd order: brainstem (medulla) –> thalamus
3rd order: thalamus –> somatosensory cortex
Explain the decussation of 2nd order neurons in touch
They decussate (cross the midline) at the level of the medulla; information is processed contralaterally within the brain
What is a sensory field?
- discrete areas of touch discrimination that fill dermatomes
- sensory fields overlap
- highly variable in size
- -size determined by # of neurons innervation a dermatome and degree of neuronal arborization
Characteristics of mechanosensory neurons
- sense touch and pain
- activated by physical distortion
- pseudounipolar
- pseudo - not unipolar; has cell body
- has continuous dendrite to axon tree
Name the 4 types of mechanoreceptor cell types
Merkel’s cells, Meissner corpuscles, Ruffini endings, and Pacinian corpuscles
Characteristics of mechanoreceptor cells
- encase mechanosensory neurons
- detect & transfer different types of skin distortion information
- sensitivity, response time, and duration of activation vary
- a single neuron innervates a single mechanoreceptor cell type
What is a nociceptor?
mechanosensory neuron that detects pain; has free nerve endings
What is a thermoreceptor?
mechanosensory neuron that detects temperature; has free nerve endings
What is the relationship between density of peripheral innervation and sensitivity?
- the higher the density of peripheral innervation, the greater the sensitivity
- ex. fingers have more neurons that skin on the back, so fingers are more sensitive than the back
Name the 5 places in the brain where sensory information is passed along
- secondary somatosensory cortex
- association cortex
- premotor cortex
- limbic cortex
- frontal cortex
Where are sensory fields organized?
in the somatosensory cortex
Explain how the somatosensory cortex is plastic
- cortical regions expand and contract in size
- use increases connectivity
- disuse decreases connectivity
Describe the 3 types of pain
1) somatic - pain perceived from peripheral cutaneous perception; thermal, mechanical, chemical
2) visceral - pain perceived from internal organ systems; referred, perceived as peripheral
3) neuropathic - pain caused by damage to PNS and CNS neurons; perceived as a burning or shocking pain
Name the 4 types of nociceptors
- thermal nociceptors
- mechanical nociceptors
- polymodal nociceptors
- silent nociceptors
Describe thermal nociceptors
- sense temperature extremes
- fast signals
- separate from thermoreceptors
Describe mechanical nociceptors
- sense extreme changes in pressure or tearing
- fast signal
Describe polymodal nociceptors
- sense thermal (hot and cold), mechanical, and chemical stimuli
- slow signal
Describe silent nociceptors
- respond to visceral disorders
- fast signal
Describe the initiation of pain signaling
- cutaneous nociceptors are activated
- inflammation releases modulatory signals (lipids - prostaglandins, thromboxanes, leukotrines, & neuropeptides)
- inflammatory molecules drive inflammation, sensitize nociceptors, & directly activate nociceptors
How do NSAIDs reduce inflammation?
-reduce the production of prostaglandins and thromboxanes
Describe the afferent connections in pain signaling
- 1st, 2nd, and 3rd order neurons
- somatosensory cortex destination
- 1st order neurons synapse in the spinal cord
- 2nd order neurons decussate in the spinal cord
- pain can be gated at the spinal cord
What is a function of silent nociceptors?
- they refer pain
- important because brain doesn’t have a map of internal organs, so the silent nociceptors allow our brain to process visceral pain by referring the pain
What is a similarity between silent nociceptors and peripheral nociceptors?
they synapse onto the same 2nd order neurons
What is the Gate Theory of pain?
- pain is gated & regulated at the level of the spinal cord; nociceptor & second order connection
- peripheral touch inhibits nociception
- no descending (brain) signaling required
- descending signals can influence spinal gating
How do opiates help the brain gate pain at the spinal cord?
- they interact with central pain receptors (brain and spinal cord) to block the transmission of nociceptive stimuli to the somatosensory cortex
- nociceptor can’t send signal to 2nd order neuron
Comparison of NSAIDs and opiates
- both can inhibit pain
- NSAIDs prevent pain peripherally
- opiates prevent pain centrally
