Neurophysiology: Neurons and Circuits Flashcards
Describe the difference between ionotropic and metabotropic receptors
- ionotropic: ligand-gated channels, fast response, direct ion flow
- metabotropic: GCPR, slower response, modulate ion channels indirectly
different classes of neurotransmitters
small-molecule neurotransmitters
amines
peptides
small-molecule neurotransmitters
small-molecular neurotransmitters (acts on ionotropic receptors, rapid responses, rapidly cleared from synaptic cleft)
amines
(released upon depolarisation and Ca2+ influx, can act on both ionotropic and metabotropic receptors, cleared by reuptake or enzymatic degradation)
peptides
(requires sustained stimulation to be released, typically acts on metabotropic receptors, thus slower and more prolonged responses, slow inactivation i.e. slower removal from synaptic cleft)
Explain graded changes in membrane potential from synaptic inputs
- synaptic inputs modulate the RMP
- can result in depolarisation (excitation) or hyperpolarisation (inhibition)
- information conveyed through chemical or electrical messages
Describe the difference between the different families of glutamate receptors
- AMPA, kainate and NMDA receptors
- subunits determine receptor chacterstics
- different subunit combinarions create various receptors
- AMPA receptors are non-selective cation channels mainly allowing Na+ influx
- NMDA contain an Mg2+ ion which blocks ions from flowing through channel so requires depolarisation before can function properly
Describe the steps in glutamate fast excitatory neurotransmission
- glutamate binds to ionotropic receptors AMPA and NMDA
- AMPA receptor activation leads to rapid Na+ influx and therefore depolarisation
- NMDA receptors allow Ca2+ entry after Mg2+ removal (triggered by teh depolarisation)
AMPA and NMDA receptors often work together for efficient transmission
Describe the different mechanisms for inactivating neurotransmitters
- recycling: glutamate removed, recycled and repackaged
- vesicular glutamate transporters (VGLUT) package glutamate into vesicles
- excitatory amino acid transporters (EATT) rapidly remove glutamate from the synaptic cleft
Describe the difference between electrical and chemical synapses
- chemical synapses: neurotransmitters released, bind to post-synaptic receptors
- electrical synapses: gap junctions physically connect neurons, allowign direct ionic passage
Describe the composition of gap junctions and the movement of ions through gap junctions
- gap junctions are composed of connexons with connexins
- connexons form a pore allowing bidirectional movement of ions
- communication of small molecules like calcium and ATP can occur through gap junctions
Discuss the Goldman and Nernst equations
- Goldman equation: calculates resting membrane potential, considering multiple ions and their permeabilities
- Nernst equation: calculates the equilibrium potential for a single ion based on its concentration
Describe how a potential is established across the neuronal membrane
- neurons exist in a state with a potential difference across their membrane
- changes in membrane potential occur due to excitatory or inhibitory inputs
- action potentials, triggered by reaching the threshold, allow long-distance communication
Identify the major constituent ions in intracellular and extracellular solution
- intracellular: High K+, low Na+, low Cl-, low Ca2+
- extracellular: low K+, high Na+, high Cl-, high Ca2+
Describe the electrical gradient, the chemical gradient and the electrochemical gradient
- electrical gradient: movement of charged particles along potential differences
- chemical gradient: movement along concentration differences
- electrochemical gradient: combined influence of electrical and chemical gradients
Define and explain why the plasma membrane is “semi-permeable”
- the neuronal plasma membrane allows some ions to pass through by restricts others
- ion channels play a crucial role in this selectivity
Explain how ions can move across the semi-permeable neuronal plasma membrane
- ions move along electrical and concentration gradients
- cell membrane is semi-permeable, allowing selective ion movement
- ion channels facilitate the passage of ions
Explain ion transporter, ion exchangers, ion pumps
- ion transporters (pumps) uses ATP to move ions agaisnt their concentration gradient
- ion exchangers utilise ion concentration gradients to move other ions without ATP
- the Na+/K+ pump, an ATPase pump, maintains ion concentration gradients
Describe how ion channels are gated and selective
- ion channels can be voltage-gated, ligand-gated or mechanically gated
- selectivity means specific ion channels allow specific ions to pass through
- channels open and close in response to various stimuli
Explain what is meant by the “equilibrium potential” of an ion
- equilibrium is reached when electrical and chemical gradients balanc
- no net movement of an ion at equilibrium
- membrane potential at equilibrium is the equilibrium potential
functional phenotype
- describes what a neuron does e.g. excites skeletal muscle cells for motor function
- identified through electrophysiology or observing its effect on post-synaptic cells
name the different types of glial cells and briefly describe their role in the nervous system
- oligodendrocytes (CNS) and Schwann cells (PNS) form myeline sheaths
- microglia act as local immune cells
- astrocytes support CNS, contribute to the blood-brain barrier and regulate ion balance
- ependymal cells create barriers and produce neural stem cells
- radial glia guid neuronal migration during development
chemical phenotype
- involves neurotransmitters produced/used (e.g. acetylcholine in motor neurons)
- identified through direct labelling, mRNA analysis, or genetic markers
combined phenotype example
cholinergic motor neuron is both functionally excitatory and uses acetylcholine
Describe the key characteristics of neurones
- Neurons are excitable cells, capable of changing their membrane potential
- classified based on their morphology, location, chemical signature and function
- information usually flows from dendrites to cell body to axon
- communicate at synapses
describe the key roles of astrocytes within the central nervous system
- regulate neurotransmission fidelity by removing excess neurotransmitters
- maintain extracellular ion homeostasis
- spatial buffering via gap junctions
- regulate blood vessel diameter and neural activity
- contribute to the blood-brain barrier
- release gliotransmitters for active communication
describe the importance of astrocytes in neuronal function and well-being
- astrocytes regulate neuronal function, blood flow and the blood-brain barrier
- actively participate in neurotransmission through gliotransmitters
- support homeostasis, ensuring proper neural activity and extracellular ion balance
describe and identify the common regions of neurones
all neurons have synapses, dendrites (mostly), cell body/soma, axo hillock and axon
describe the direction of the flow of information in neurons
- information flows from dendrites to cell body to axon
- special cases dendrites are skipped
determine the output of a simple neural circuit
- output is the sum total of all inputs within the circuit
- excitatory neurons increase post-synaptic cell activity
- inhibitory neurons decrease post-synaptic cell activity
explain the difference between excitatory and inhibitory neurons
- excitatory neurons
- increase activity of post-synaptic cell
- release neurotransmitters that enhance neural activity
- inhibitory neurons
- decrease activity of post-synaptic cell
- release neurotransmitters that suppress neural activity
Ion channel fundamentals:
- Determinants: Electrochemical gradient (chemical and electrical gradients).
- Effect on Membrane Potential: Inhibitory ion channels lead to hyperpolarization.
- Equilibrium Potential: Membrane potential with no net ion movement through open channels.
- GABA’s Dual Role: Context-dependent excitatory or inhibitory function.
Inhibitory neurons:
- Role: Coordinate muscle groups, selective activation, and modulation of neural activity.
- Neurotransmitters: GABA and glycine.
- Differentiation: Receptors recognize subtle structural differences.
GABA’s dual role
GABA is not always inhibitory; in some contexts, such as the enteric nervous system of invertebrates, it can be excitatory. This shift is attributed to changes in GABA’s intracellular concentration during maturation.
Explain the concept of equilibrium potential
Equilibrium potential, also known as reversal potential, is the membrane potential at which there is no net movement of a specific ion through its open channel. The electrochemical gradient, determined by the Nernst equation, dictates the equilibrium potential for an ion.
Describe the effect of activating inhibitory ion channels on membrane potential
Activating inhibitory ion channels, such as GABA and glycine receptors, leads to hyperpolarization of the membrane potential.
This inhibitory effect results from the movement of chloride ions, which makes the interior of the cell more negative.
Explain what determined the movement of ions through an ion channel
The movement of ions through an ion channel is determined by the electrochemical gradient, which includes both the chemical concentration gradient and the electrical potential gradient across the cell membrane.
The Nernst equation describes the equilibrium potential for an ion, determining the direction of ion movement.
Identify the major fast inhibitory neurotransmitters
The major fast inhibitory neurotransmitters are GABA (gamma-aminobutyric acid) and glycine.
Describe and identify the difference between GABA and glutamate
GABA and glutamate are both neurotransmitters, but GABA is the principal fast inhibitory neurotransmitter, while glutamate is the principal fast excitatory neurotransmitter. The structural difference between them lies in a carboxyl group, and GABA is synthesized from glutamate by the enzyme glutamic acid decarboxylase (GAD).
Describe the mechanism that allows receptors to differentiate between very similar molecules
Receptors differentiate between similar molecules through their specific structural configurations and binding sites.
Even though GABA and glutamate are structurally similar, the receptors have evolved to recognize subtle differences, allowing for the precise and selective binding of neurotransmitters to their respective receptors.
Describe and explain why inhibitory neurons are important in neural circuits
Inhibitory neurons play a crucial role in neural circuits by causing hyperpolarization, which inhibits or prevents the firing of neurons.
This allows for the coordination of antagonistic muscle groups, selective activation of specific behavioural pathways, and modulation of neural activity, contributing to the overall fine-tuning and control of neural circuits.
Identify the enzymes and transporters specific to catecholamine
- the enzymes used in catecholamine pathways are tyrosine hydroxylase, DOPA decarboxylase, DBH and PNMT
- transporters used are DAT (an Na+ co-transporter that takes up dopamine), NA/A (NET also a Na+ co-transporter that take sup dopamine) and vesicular monoamine transporter (VMAT that takes up all monoamines)