Neurons Pyramidal neurons in mouse cerebral cortex expressing green fluorescent protein. The red staining indicates GABAergic interneurons. MBL, Woods Hole R Cheung MSc Bioelectronics: PGEE11106 1
Neuron The functional and structural unit of the nervous system There are many different types of neurons, but most have certain structural and functional characteristics in common Dendrite Axon Node of Ranvier Axon terminal Hillock Axon Schwann cell Nucleus Myelin sheath R Cheung MSc Bioelectronics: PGEE11106 2
Function of Neurons Neurons are excitable cells specialized to conduct information from one part of the body to another via electrical impulses conducted along their axons. Communication Model Medium: AXON Sender Message: ACTION POTENTIAL Receiver R Cheung MSc Bioelectronics: PGEE11106 3
Membrane Potentials: Signals Neurons use changes in membrane potential to receive, integrate, and send information. Two types of signals are produced by a change in membrane potential: Graded potentials (shortdistance) Action potentials (longdistance) R Cheung MSc Bioelectronics: PGEE11106 4
Resting Axon Membrane Potential Resting Neuron : Membrane is polarized. Inner, axoplasmic, side is negatively charged. All gatedsodium and potassium channels are closed. 70 mv The membrane potential is always given as the intracellular potential relative to the extracellular potential which is arbitrarily defined as zero. R Cheung MSc Bioelectronics: PGEE11106 5
Graded Potentials Shortlived, local changes in membrane potential Currents decrease in magnitude with distance Their magnitude varies directly with the strength of the stimulus The stronger the stimulus the more the voltage changes, the farther the current goes, and more likely to initiate action potentials stimulus Depolarization Spread of Depolarization R Cheung MSc Bioelectronics: PGEE11106 6
Action Potentials (APs) Suprathreshold stimuli cause voltagegated Na channels to open to produce depolarizing currents The AP is a brief reversal of membrane potential with a total amplitude of ~100 mv (from 70mV to 30mV) APs do not decrease in strength with distance AllorNothing action potentials either happen completely, or not at all R Cheung MSc Bioelectronics: PGEE11106 7
Signals Carried by Neurons Appropriate stimulus applied to the resting axon triggers nerve impulse/action potential Membrane becomes negative externally High [Na ] High [K ] Resting Membrane At the leading edge of the impulse, fast sodium gates open. The membrane becomes more permeable to Na ions and an action potential occurs. [Na ] Depolarization and generation of the nerve impulse R Cheung MSc Bioelectronics: PGEE11106 8
Signals Carried by Neurons Propagation of the AP Repolarization [K ] [Na ] [Na ] Depolarization As the action potential passes, slow potassium gates open, allowing K ions to flow out. The action potential continues to move along the axon in the direction of the nerve impulse. R Cheung MSc Bioelectronics: PGEE11106 9
The Dipole Field due to Current Flow in an Axon at the Advancing Front of Depolarization. R Cheung MSc Bioelectronics: PGEE11106 10
Hyperpolarization The slow K gates remain open longer than needed to restore the resting state. This excessive efflux causes hyperpolarization of the membrane. The axon is insensitive to stimulus and depolarization during this time. R Cheung MSc Bioelectronics: PGEE11106 11
Role of the SodiumPotassium Pump Repolarization restores the resting electrical conditions of the axon, but does not restore the resting ionic conditions. Ionic redistribution is accomplished by the sodiumpotassium pump following repolarization. R Cheung MSc Bioelectronics: PGEE11106 12
Refractory Periods Absolute Refractory Period: Time between opening and closing of the Na activation gates. The axon cannot respond to another stimulus. Relative Refractory Period: Follows the absolute refractory period. Na gates are closed, K gates are open and repolarization is occurring. Only a strong stimulus can generate an AP. 30 mv 0 Absolute RP Relative RP 55 mv 70 mv stimulus R Cheung MSc Bioelectronics: PGEE11106 13
Axon Conduction Velocities Conduction velocities vary widely among neurons, determined mainly by: Axon Diameter the larger the diameter, the faster the impulse (less resistance) Presence of a Myelin Sheath myelination increases impulse speed (Continuous vs. Saltatory Conduction) R Cheung MSc Bioelectronics: PGEE11106 14
Saltatory Conduction Gaps in the myelin sheath between adjacent Schwann cells are called nodes of Ranvier. Voltagegated Na channels are concentrated at these nodes. Action potentials are triggered only at the nodes and jump from one node to the next. Much faster than conduction along unmyelinated axons. Axon Myelin sheath [Na ] [Na ] Node of Ranvier R Cheung MSc Bioelectronics: PGEE11106 15
Information Transfer at Synapse As the impulse reaches the axon terminals the signal is relayed to target cells at specialized junctions known as synapses. Arrival of impulse at synapse opens Ca 2 channels. Neurotransmitter is released into the synaptic cleft via exocytosis. Neurotransmitter crosses the synaptic cleft and binds to receptors on the postsynaptic neuron. Postsynaptic membrane permeability changes due to opening of ion channels, causing an excitatory or inhibitory effect. R Cheung MSc Bioelectronics: PGEE11106 16
Synaptic Transmission An AP reaches the axon terminal of the presynaptic cell and causes V gated Ca 2 channels to open. Ca 2 rushes in, binds to regulatory proteins & initiates neurotransmittier (NT) exocytosis. NTs diffuse across the synaptic cleft and then bind to receptors on the postsynaptic membrane and initiate some sort of response on the postsynaptic cell. R Cheung MSc Bioelectronics: PGEE11106 17
Neurotransmitter Removal NTs are removed from the synaptic cleft via: Enzymatic degradation Diffusion Reuptake R Cheung MSc Bioelectronics: PGEE11106 18
Effects of the Neurotransmitter Different neurons can contain different NTs. Different postsynaptic cells may contain different receptors. Thus, the effects of an NT can vary. Some NTs cause cation channels to open, which results in a graded depolarization. Some NTs cause anion channels to open, which results in a graded hyperpolarization. R Cheung MSc Bioelectronics: PGEE11106 19
Excitatory and Inhibitory Neurotransmitters Typically, a single synaptic interaction will not create a graded depolarization strong enough to migrate to the axon hillock and induce the firing of an AP However, a graded depolarization will bring the membrane potential closer to threshold. This is referred to as an excitatory postsynaptic potential. Graded hyperpolarizations bring the membrane potential farther away from threshold and thus are referred to as inhibitory postsynaptic potentials. Whether a transmitter is excitatory or inhibitory depends on its receptor. R Cheung MSc Bioelectronics: PGEE11106 20
Excitatory and Inhibitory Neurotransmitters Acetylcholine is excitatory because its receptor is a ligandgated Na channel. GABA is inhibitory because its receptor is a ligandgated Cl channel. Other transmitters (e.g. vasopressin, dopamine) have Gproteinlinked receptors. Effects depend on the signal transduction pathway and cell type. R Cheung MSc Bioelectronics: PGEE11106 21
Temporal Summation One Excitory Postsynaptic Potential (EPSP) is usually not strong enough to cause an Action Potential. However, EPSPs may be summed: Temporal summation the same presynaptic neuron stimulates the postsynaptic neuron multiple times in a brief period. The depolarization resulting from the combination of all the EPSPs may cause an AP. Spatial summation multiple neurons all stimulate a postsynaptic neuron resulting in a combination of EPSPs which may yield an AP. 30 mv 0 55 mv 70 mv EPSPs stimulii R Cheung MSc Bioelectronics: PGEE11106 22
Synaptic Organization Communication between neurons is not typically a onetoone event. Sometimes a single neuron branches and its collaterals synapse on multiple target neurons. This is known as divergence. A single postsynaptic neuron may have synapses with as many as 10,000 presynaptic neurons. This is convergence. Divergence Convergence R Cheung MSc Bioelectronics: PGEE11106 23
Videos of Neurons in Action R Cheung MSc Bioelectronics: PGEE11106 24