neuro - synapses + ion channels
synapses and sensory systems
chemical vs electrical synapses
most synapses are chemical and use neurotransmitters
recent evidence shows electrical synapses play huge role in vertebrate and invertebrate brains
ions flow directly between cells
less known about electrical synapses
electrical transmission is much simpler
one of the main differences → bidirectional
electrical synapses → direct connection by gap junction channels
chemical synapses have a larger synaptic cleft than electrical (~10x bigger)
chemical transmission is slower
action potential reaches presynaptic terminal → opens Ca+ gated ion channels → triggers release of synaptic vesicles containing neurotransmitters
some synapses are a mixture of chemical and electrical
chemical synapses can synapse onto electrical synapses and mediate their behaviour
main features of chemical synapses
slower transmission
more steps in process
vesicles at presynaptic terminal
synaptic delay (0.3-3)
cleft ~20-30nm
neurotransmitters bind to postsynaptic receptors and generate electric or chemical change in postsynaptic membrane
ionotropic receptor - fast, short-lived change in membrane potential - depolarisation or hyperpolarisation - by directly changing permeability to ions
metabotropic receptor - slower, long lasting modulatory effect
in CNS → most synapses occur on neuronal dendrites
mushroom-shaped protrusions - dendritic spines
adaptive advantage of chemical synapses
amplify current flow
each vesicle contains a few thousand molecules of transmitter
can open many channels and amplify postsynaptic current
can be excitatory or inhibitory
electrical synapses are nearly always excitatory
one-way communication
most electrical synapses are two-way
modifiable
use and circumstance can make them stronger
disuse can make them weaker
plasticity important for nervous system development and learning
sensory systems
vertebrates vs invertebrates (arthropods)
all invertebrate axons are unmyelinated
distance to CNS much shorter so don’t need?
vertebrates have ends of sensory neuron in skin
arthropods have sensillum through hard cuticle
each sensillum has a sensory neuron at its base
axon runs to CNS
typical arthropod sensillum = very small - hard to study using electrophysiological techniques
another type of mechanoreceptors = proprioceptors
detect position and movement of joints
much bigger and can be studied electrophysiologically
photoreceptors in insect compound eyes
eye surface made up of lots of lenses
behind lens = ommatidium
some insects have thousands of ommatidea
compound eyes can be apposition or superposition
most diurnal insects have apposition eyes
most night-flying insects have superposition eyes
summary:
stimulus opens sodium channels in receptor cells
sodium enters and generates receptor potential
receptor potential reaches synapse
transmitter released
ion channels and receptor potentials
stimulus transduction
stimuli must be:
collected at boundary membrane
transduced into messages within organism
fluidity of membranes is important in sensory systems
proteins shuttled into plane of membrane to relay signals
allostery
process by which biological macromolecules (e.g. membrane proteins) transmit effect of binding at one site to another functional site, allowing for activity regulation
in membranes → stimulus results in protein changing shape → membrane potential (transduction)
weak secondary and tertiary bonds → higher structure of protein easily shifted from one state to another
allosteric activation → conformational change reveals active site on protein surface
allosteric inhibition → conformational change distorts active site
G protein-coupled receptors
seven transmembrane domains
third intracellular loop and C-terminal sequence are involved in G-protein recognition
phosphorylation sites on C-terminal involved in desensitisation
occurs when receptor is overexposed → becomes unresponsive
desensitisation results in sensory adaptation
when response to constant stimulus falls off over time, no longer aware of it
GPCRs → phosphorylation of hydroxyl groups of amino acids at C-terminal alters 3D conformation of receptor
deactivates it over time
sensitivity restored when tail is dephosphorylated by phosphatase enzymes in cytosol
1 - binding of ligand activates GPCR
2 - conformational change causes it to release its bound GDP → replaced by cytosolic GTP
G-protein splits into alpha subunit and beta-gamma subunit complex
3 - alpha subunit travels to membrane bound effector molecule → often results in release of second messenger into cytosol
4 - alpha subunit GTP is hydrolysed to GDP → mechanism switched off and conformation changed back → binds back to beta-gamma complex and reattaches to deactivated receptor
effectors and second messengers
adenylyl cyclase (ACs)
cAMP second messenger
inhibit or activate enzymes, receptors or channel proteins
phospholipase C-β (PIP2-phospholipase)
inositol triphosphate (IP3) and diacylglycerol (DAG) second messengers
i remember this bit!
IP3 diffuses into cytosol to interact with receptors in ER → leads to release of calcium ions
DAG stays in membrane → interacts with protein kinase C (PKC) and transient receptor protein (TRP)
these reactions are Ca2+ dependent
PKC activates proteins
G-proteins provide flexible means of transforming external signals into second messenger
transient receptor potential (TRP) channels
most ancient type of cell sensors
TRP channels include all three types of activation → direct, ligand-gated and voltage-gated
tertiary structure includes 6 transmembrane domains
quaternary structure → four 6TM subunits grouped around central pore
directly involved in sensing mechanical and thermal stimuli
allow calcium and sodium ions to flow inward down conc gradient → depolarising membrane and causing receptor potential
rapidly shut by cytoplasmic Ca2+
ligand-gated ion channels (LGICs)
most significant in sensory systems are those in olfactory and photoreceptor cells
similar structure to TRP channels
voltage-gated ion channels (VGICs)
activated by changes in membrane potential
differ in the ions they allow to pass
any change in potential gradient results in conformational change in membrane bound voltage-sensitive proteins
voltage-sensitive Na+ channel very important
responsible for rising phase of action potential
key in excitable nerve and striated muscle tissues
single big polypeptide with 4 homologous domains, each with 6 transmembrane helices
when voltage across membrane drops below threshold, channel opens for ~1ms → allows Na+ ions carrying ~2 pico Amperes (pA) of current to pass
membrane depolarised → channel won’t open
as an excitable membrane is depolarised → more and more sodium channels open
influx depolarises membrane → action potential
sensory adaptation
two systems - rapidly adapting and slowly adapting response
rapidly adapting → rapid burst of activity in sensory fibre when stimulus turned on, quickly falls back toward zero until stimulus turned off → marked by another rapid burst of activity
slowly adapting → rapid burst of activity when stimulus turned on, declines slowly over time and not to zero
remains at plateau until stimulus turned off
both cases → frequency of initial burst of impulses signals intensity of stimulus
different biophysical causes for adaptation
e.g. result of methylation of receptor transducer proteins in bacterial chemosensitivity
animal G-protein systems → result of phosphorylation which occurs on cytosolic C terminus
overview
Stimulus Transduction:
Stimuli collected at boundary membrane and transduced into organismal messages.
Membrane fluidity crucial; proteins shuttle within the membrane to relay signals.
Allostery:
Biological macromolecules transmit binding effects from one site to another.
Membrane proteins undergo conformational changes for stimulus transduction.
Allosteric activation reveals active sites, while inhibition distorts them.
G Protein-Coupled Receptors (GPCRs):
Seven transmembrane domains.
Third intracellular loop and C-terminal involved in G-protein recognition.
Desensitization occurs via phosphorylation sites on the C-terminal.
GPCR Activation:
Ligand binding activates GPCR.
Conformational change triggers GDP release, replaced by cytosolic GTP.
G-protein splits; alpha subunit activates effector molecules.
GTP hydrolysis deactivates mechanism.
Effectors and Second Messengers:
Adenylyl cyclase (ACs) produces cAMP.
Phospholipase C-β generates IP3 and DAG.
TRP channels involved in sensing mechanical and thermal stimuli.
Transient Receptor Potential (TRP) Channels:
Include direct, ligand-gated, and voltage-gated activation.
Permit inward flow of calcium and sodium ions, depolarizing the membrane.
Ligand-Gated Ion Channels (LGICs):
Significant in olfactory and photoreceptor cells.
Similar structure to TRP channels.
Voltage-Gated Ion Channels (VGICs):
Activated by changes in membrane potential.
Different ions allowed to pass; crucial in action potential generation.
Sensory Adaptation:
Rapidly and slowly adapting responses.
Frequency of impulses reflects stimulus intensity.
Biophysical causes include methylation of receptor transducer proteins and phosphorylation in animal G-protein systems.
sensory inhibition
neurotransmitters
ALT
two major types of neurotransmitter
small molecule neurotransmitters → mostly amines and amino acids
neuropeptides
many neurotransmitters have different modes of action depending on the receptor they are binding to
ACh is excitatory in skeletal muscle but inhibitory in heart muscle
ACh binds to two types of receptors → nicotinic and muscarinic
nicotinic → depolarising post synaptic potential
muscarinic → hyperpolarising post synaptic potential
amino acids can be neurotransmitters → glutamate is main excitatory neurotransmitter in CNS
can bind to AMPA receptors for fast response, NMDA for slow response
both excitatory
GABA and glycine are also amino acids → main inhibitory neurotransmitters in CNS
EPSP = Excitatory post-synaptic potential
driven by influx of cations into neuron
key point → excitation vs inhibition depends on neurotransmitter and post-synaptic receptor
importance of inhibition → lateral line system
openings on body surface that connect into canals → nerves from canals to brain
system found in many organisms
e.g. elasmobranchs, teleost fish, amphibian tadpoles, adult aquatic amphibians
basic structure similar across all of them
aquatic Xenopus toad
lateral line system runs from head along length of body
bundles of hair (cilia) cells with nerves innervating base
cilia inject into cupula → jelly-like structure
two types of cilia → long kinocilium + bundle of stereocilia
movement of cilia controls receptor potential of hair cells + transmitter release from synapse at base
hair cell then synapses onto afferent nerve ending
afferent = going to the brain
efferent = coming out of the brain
ALT
basic lateral line structure
simplest form = free neuromast
skin is slightly raised where hair cells in cupula stick out above surface
more complicated model = pit organs
structure is placed into a pit which offers it more protection
most complex = canal organs
clusters of cupuli are in a canal under the skin with a pore through the surface
how do lateral line organs work?
recordings have been made from afferent nerves → looked at patterns of impulses
tube inserted into canal → water could be flowed into canal in either direction → measured afferent nerve activity from lateral line
no movement → steady pattern of impulses at rest
allows for level of impulses to go up or down → system can respond to change
resting level of neurotransmitter being released so can increase or decrease
cupula bends towards kinocilium → afferent nerve increases impulse frequency
hair cell is excited and releases more neurotransmitter
cupula bends away from kinocilium → frequency of impulses falls (inhibition)
cupula returns to resting position → impulses return to normal
lateral line - efferent control
important to separate biologically important signals from noise
e.g. when a fish moves it creates a disturbance in the water - that could be detected by the lateral line system → unwanted irrelevant signals
efferent signal sent to hair cell upon initiation of motor action
results in inhibition → stops hair cell getting over stimulated
means the animal can still pick up important sensory signals from environment
allows animal using lateral line system to retain perception of motion stimuli without interference created by its own movements
efferent control mechanism
acetylcholine binds to nicotinic acetylcholine receptor
calcium enters → activates small conductance (SK) channel
potassium leaves cell
membrane potential hyperpolarised (more negative)
discovered by Dawkins, Keller and Sewell (2005)
as soon as an animal’s activity stops → efferent inhibition stops
roles of lateral line receptors
related to vibration, pressure waves or current in water
detection of prey or predators
allows some fish and tadpoles to capture insects → detect vibrations at water surface
assess status of conspecifics
Mexican blind fish → very good at distinguishing shapes in environment using lateral line
electroreception
passive electroreception → animal senses weak bioelectric fields generated by other animals, uses it to locate them
active electroreception → animal senses surrounding environment by generating electric fields and detecting distortions in these fields using electroreceptor organs
passive detection → dogfish
spotted dogfish can locate a flatfish buried in the sand with no visual cues
can locate fish covered by agar chamber → conducts electricity but not mechanical/chemical cues
cannot locate fish covered by polythene sheet → blocks electrical cues
attacked two electrodes hidden in sand → presented electrical cues similar to flatfish
skate → ampullary system nerves
canals opening at body surface in addition to lateral line canals
come together in clusters
form the ampullae system → collectively known as Ampullae of Lorenzini
nerves that carry this sensory electroreceptor information to the brain = buccal and mandibular nerves
if you cut the nerves leading from the ampullae to the brain → can no longer respond to electrical signals
electrical signal conducted along ampullae using electrically conductive jelly
walls of ampullae have modified hair cells with single cilium → respond to electrical currents in canal
excited (negative voltage)→ release neurotransmitter onto afferent nerve
positive voltage → decrease in neurotransmitter release onto afferent nerve
ALT
have resting neurotransmitter impulse like in lateral line system
amount of neurotransmitter released from hair cell increases or decreases according to size and polarity of electrical stimulus
elasmobranch sensory epithelium (SE)
layer of receptor cells (RC) and support cells (SC)
tight junctions between cells → high electrical resistance barrier
between lumen of ampulla and base of RC
stops electrical charge from leaking out
difference between lumen voltage (V) and reference voltage (VREF) → stimulates hair cells on receptors, controls release of neurotransmitter onto primary afferent neurons
gating inhibition - control of pain
painful stimuli come in through small sensory axons (unnmyelinated)
axons enter dorsal horn → release neurotransmitter called substance P
neuropeptide
substance P excites projection neurons which travel to other side of spinal cord
this contralateral movement (movement to the other side) is called decussation
this is why one side of the brain processes sensory information from the opposite side of the body
evolutionary significance unclear
ALT
signals of pain perception can be altered by other stimuli
one sensory input can influence another
if you rub your skin to try lessen pain, this information is carried by a different sensory neuron
mechanoreception is carried by large myelinated neurons → come into spinal cord through dorsal side, up to brain
incoming axon from the large myelinated neuron has a side branch → excitatory synapses with inhibitory neurons in dorsal horn
these inhibitory neurons inhibit projection neurons carrying pain stimuli
signal doesn’t reach spinothalamic tract at same intensity
these systems close a gate on pain pathway → hence name of gating inhibition
do this by releasing enkephalin → binds to opioid receptors → hyperpolarises projection neurons by increasing potassium leaving cell
