CSB332 Lecture 9, 10, 11 Notes

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Cell and Systems Biology
Francis Bambico

CSB332 Lecture 9 Slide 3 - Electrical impulses flow from first order sensory (afferent) neurons in the PNS to second order sensory neurons located within the spinal cord. The signal is eventually relayed to the thalamus, which is the major sensory relay station of the nervous system. From there, information is delivered to different areas in the brain for further cortical and cognitive processing. - One of the functions of cognitive processing is to be able to compare novel information with information already stored in different areas of the cerebral cortex. Cognitive processing allows the organism to activate the appropriate behavioural program in response to the stimulus encountered. The behavioural output is encoded in outgoing electrical impulses that propagate along motor neurons and motor fibres forming the cortical spinal tract. The signals terminate in the NMJ. - The flow of information from one neuron to another is called synaptic transmission. Electrical signals are communicated or transmitted from one region of the PNS until the signals get to the CNS. Once it gets to the CNS, there is going to be cognitive processing. cognitive processing refers to comparing information that is already stored in the brain with new information that has just been received. This will generate a response to the stimulation received. The motor response will be translated into behaviour. - When a signal flows from one type of neuron to another, they typically change in terms of the type of signals. The pattern of transmission of the signals follows a series of transformations from graded potentials to action potentials. When the impulses reach another region of the brain, then the same series of transformations occur. - The neurons of the brain act like AD converters (analog-to-digital). Neurons convert analog signals (e.g., graded potentials) in the form of continuous values that are disproportionate to intensity or magnitude of the stimulation. Eventually, at the axon hillock or the AIS, the analog signal gets converted to a digital signal (e.g., action potential). An action potential is a digital signal because an action potential generates in an all or none fashion. The neuron either fires or not at all (e.g., 1 = yes firing, 0 = no firing). Slide 4 - In the PNS, environmental stimuli (e.g., light, sound, odorant chemicals, touch, pain mediating stimuli, temperature, etc.) are converted to electrical signals called receptor potentials. This conversion is termed sensory transduction and occurs in two subtypes of receptors. - Short receptor cells have short axons. The distance between the receiving area and the synaptic region is less than 0.1 mm. Short receptor cells do not generate action potentials, rather they use graded or electrotonic potentials. They release neurotransmitters tonically or continuously. - Long receptor cells are typically pseudounipolar cells. Pseudounipolar cells have cell bodies that project two segments of axons. One segment extends toward the receiving area. The other segment extends toward the second order sensory neurons. The distance between the receiving area and the terminal axons is more than 0.1 mm. - The first step in transmission occurs in sensory receptors. An ecological environmental stimulus gets converted into electrical impulses that can be understood and propagated into the nervous system through a process called sensory transduction. Sensory transduction occurs in different types of sensory receptors that are present in different parts of the body. There are two types of sensory receptors. - Short receptors typically either do not have axons or have very short axons. The distance from the receiving region and the synaptic region is less than 0.1 mm. The release of neurotransmitters from sensory receptors is based upon whether the membrane potential of the receptor is depolarized or hyperpolarized. Neurotransmitters being released from these receptors are continuous that is modulated by whether the receptor is depolarized or hyperpolarized. Depolarization may result in a decrease in the release of neurotransmitters and hyperpolarization may result in an increase in the release of neurotransmitters, or vice versa. - For long receptors, the distance from the sensory receiving area to the synaptic region is more than 0.1 mm. They are considered pseudounipolar cells, which have two bifurcated axons projecting from the cell body. One region of the axon is directly connected to the sensory area. The other region of the axon will comprise your terminal axons that would synapse to the second or third order neurons. Slide 5 - Receptors that mediate mechanoreception, pain, temperature, proprioreception in the limbs and trunk, proprioreception in the jaw, and olfaction are all examples of long receptor cells. - Receptors that mediate gustation (taste buds), audition (hair cells), and vision (photoreceptors) are all examples of short receptors. Slide 6 - The molecular receptors for odorants are found in sensory cilia that project into the mucus layer of olfactory epithelium. Depolarizing receptor potentials in the long receptors gives rise to action potentials that propagate along the olfactory receptor neuron’s axon into the CNS. - Odorant molecules bind to specific GPCR in the plasma membrane of the sensory cilia. This frees the alpha subunit to activate AC, which increases the concentration of cAMP. This causes non- selective cation channels to open, which depolarizes the membrane. Ca2+-gated current can enhance this effect. - Other pathways may involve the activation of another enzyme called PLC. The consequent increase in IP3 concentration acts directly on plasma membrane Ca2+ channels. - The sensory area is located on sensory cilia, which are thread-like projections that emanate from the cell body. Chemical odorants are received by receptors located along the sensory cilia. These receptors are typically metabotropic receptors, which are coupled to G proteins and many other signaling molecules inside the cell, so that when these receptors get activated by chemical odorants, the receptor will change its conformation, resulting in the activation of many signaling molecules in the cell, resulting in changes in the conductance of ion channels. - This type of receptor results in an increase in calcium conductance (calcium influx) and an increase chloride conductance (chloride efflux) resulting in the depolarization of the cytosolic environment, leading to the depolarization of the cell, and resulting in the generation of an action potential. CSB332 Lecture 10 Slide 8 - Electrical impulses generated in higher neural pathways (in second and third order sensory neurons, in interneurons, and in motor neurons in the cerebral cortex) occur via postsynaptic receptors that produce graded potentials that summate as they travel towards the axon hillock/axon initial segment. Slide 9 - In electrochemical synapses, presynaptic excitatory axons release excitatory neurotransmitters (e.g., glutamate) that activate excitatory postsynaptic receptors. Activation of excitatory postsynaptic receptors would generate EPSPs. - Presynaptic inhibitory inputs release inhibitory neurotransmitters (e.g., GABA). These neurotransmitters activate inhibitory postsynaptic receptors that would then generate IPSPs. - All generated EPSPs and IPSPs would then travel towards the axon initial segment or the axon hillock. As they travel, they will summate. o Temporal summation occurs when two or more EPSPs or IPSPs are generated almost at the same time or close to each other in time. o Spatial summation occurs when two or more EPSPs or IPSPs are generated by two or more neighbouring postsynaptic regions or close to each other in location. - When the sum of EPSPs and IPSPs at the AIS reaches a threshold of excitation, then the neuron will fire an action potential. If it is below the threshold of excitation, then the neuron will not fire an action potential. - In higher order neurons in the brain and the spinal cord, you won’t find any sensory receptors. Synaptic transmission occurs via postsynaptic receptors. Postsynaptic receptors are expressed on the cell body of neurons. There are two types of postsynaptic receptors: ionotropic and metabotropic. o An ionotropic receptor is an ion channel itself. When a ligand binds to an ionotropic receptor, it allows the influx or efflux of ions. o A metabotropic receptor does not form a pore, but are simpler in terms of function. They are composed of a continuous sequence of amino acids producing seven transmembrane domains. It is called a serpentine receptor because the structure looks like a serpent. The N-terminus is located outside of the cell. The C-terminus is located inside the cell. They have special regions within the intracellular domain that interacts with G proteins. This is why metabotropic receptors are called G proteins. Their intracellular domain directly interacts and binds G proteins. There are also other domains that are sensitive to phosphorylation. - When ionotropic or metabotropic receptors are activated by a ligand, they produce two types of current: EPSC or IPSC. It depends on the type of receptor. o If an ionotropic receptor (e.g., GABAergic receptor) is a chloride channel, then activation of the receptor results in the generation of IPSPs. If the ionotropic receptor is an ion channel that is permeable to sodium or calcium, then activation of the receptor results in the generation of EPSPs. Slide 10 - As opposed to chemical synapses, postsynaptic receptor potentials are not generated in electrical synapses (gap junctions). Current flows from the cytosolic environment of neuron to the cytosolic environment of the other neuron via specialized hemichannels called connexons. This type of transmission is called direct synaptic transmission. - Connexons interconnect the cytoplasmic environment of two or more neurons. Each connexon or hemichannel is composed of six subunits called connexins. A connexin is composed of four membrane spanning domains. - Electrical synapses (gap junctions) allow for the continuous flow of current from one neuron to another. This is how current is transmitted in electrochemical signals. Slide 11
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