5001Neuro Foundations for Neuroscience (1).pdf

1 Basic terms Central Nervous System (CNS) – brain and spinal cord Peripheral Nervous System (PNS) Ganglion – group of neuronal cell bodies with similar function, located outside the CNS. Can be either sensory or motor. Nucleus – group of neuronal cell bodies with similar function, located within th...

1 Basic terms Central Nervous System (CNS) – brain and spinal cord Peripheral Nervous System (PNS) Ganglion – group of neuronal cell bodies with similar function, located outside the CNS. Can be either sensory or motor. Nucleus – group of neuronal cell bodies with similar function, located within the CNS. Autonomic Nervous System (ANS) – 1) sympathetic, 2) parasympathetic Morphology Three basic types of neurons. 2 3 Myelin (lipids and proteins): made by Schwann cell in the PNS and oligodendrocytes in the CNS. Schwann cells myelinate one axon. Oligodendrocytes can myelinate multiple axons. Myelin components different between PNS and CNS. 4 Fiber types 5 Axon – a closer look Axon transport Anterograde, aka orthograde: Kinesin ATPase – fast, dense core vesicles (contains neuropeptides), mitochondria Slow, unknown mechanism. Neurofilaments, microtubules components, e.g., tubulin Retrograde: Dynein ATPase: organelle degradation, e.g., mitochondria, factors taken up at presynaptic terminal, normal, e.g., growth factors, e.g. nerve growth factor (NGF), pathological, e.g., rabies virus, bacterium Clostridium. 6 Resting Membrane Potential (RMP) 2 factors determine resting membrane potential. 1) permeability (sorta like conductance [conductance is the inverse of resistance for movement of charged particles]) of the membrane to a given ion. 2) concentration gradient of that ion. Key terms: electrical potential and capacitance (ability to separate charge) 7 Nernst Equation: 61mV E= z [X]outside log [X]inside An estimate of the resting cell membrane potential (RMP) Chord conduction equation: Em = gKEK gN aEN a gC lEC l + + Sg Sg Sg Sg = (gK +gNa + gCl) Normally the cell membrane is most permeable to potassium, so potassium concentration gradient has the most influence on RMP. Goldman Equation aka, Goldman-Hodgkin-Katz Equation Em = 61log Pk[K+]o + PNa[Na+]o + PCl[Cl-]i Pk[K+]i + PNa[Na+]i + PCl[Cl-]o 8 Action Potential Suppose we have the following cell: 145mM 15mM Na+ 5mM 140mM K+ 110mM 10mM Cl- Proteinsmeasured E = -70mV If only Na+ channels open up and remain open. Assume ENa= +60 mV. 60 mV 0 mV -70 mV 9 If only K+ channels open up and remain open. Assume EK = -88 mV 60 mV 0 mV -70 mV -88 mV If both Na+ and K+ channels open up at the same time and remain open. 60 mV 0 mV -70 mV -88 mV 10 If Na+ channels open up first, then after a certain time lapse the K+ channels open, and both channels remain open. 60 mV 0 mV -70 mV If Na+ channels open up then after a certain time they close, yet before they close, K+ channels open up for a certain time and remain open even after the Na+ channels close and then after a certain time they also close. 60 mV 0 mV -70 mV 11 Voltage sensitive channels (voltage gated channels) 12 Depolarization: An action potential can be generated only if a critical number of Na+ channels are recruited. Voltage sensitive Na+ channels open up in a range of membrane potential (-70mV to +40mV). Threshold is achieved only when enough channels are open at the same time. When the stimulus is larger than the threshold, the size and shape of the action potential does not change. As far as action potentials go it's all or none. 13 Repolarization: caused by voltage sensitive K+ channels (these are different channels from the K+/Na+ leaking channels). These voltage sensitive channels begin to open up as the membrane potential rises above -90 mV (this varies depending upon cell type). They open up more slowly than the activation gates of the Na+ channels. Repolarization occurs within a few msec. Neuroscientists use tetraethylammonium (TEA) to selectively block voltage sensitive K+ channels. Hyperpolarization: voltage sensitive K+ channels are slow to close after repolarization; therefore, the membrane potential becomes more negative than the resting potential. How would TEA affect the voltage change profile of an action potential? 60 mV 0 mV -70 mV 14 Presynaptic terminal and release of neurotransmitters Mechanism for synaptic release of NT from vesicles. Action potential travels down the axon and the depolarization of the membrane potential at the presynaptic terminal opens up voltage sensitive Ca+2 channels. This influx of Ca+2 activates proteins in the presynaptic terminal to move the NT vesicles to the synaptic membrane where they fuse with it releasing their NT's. Upon binding to the post-synaptic membrane receptors, they will either cause that membrane to become more positive (excitatory postsynaptic potential [EPSP]) or more negative (inhibitory postsynaptic potential [IPSP]). Vesicles with neurotransmitters pulled towards distal membrane v-SNARES t-SNARES Clinical point: Lambert-Eaton myasthenic syndrome (LEMS) is a condition in which the body's immune system attacks certain isoforms of voltage sensitive calcium channels at the presynaptic terminal compromising release of acetylcholine (ACH). Antibodies are also thought to interfere with the vSNARE and t-SNARE interaction of this motor neurons. It is most often seen in people with small cell lung cancer or other cancers, but it can also occur in people without cancer. 15 Summary of events of action potential and depolarization of the postsynaptic terminal. 16 How does an actional potential get started? Ionotropic receptors: ligand binds to the receptor and the ion channel changes shape Example: nicotinic receptors (nACHR) on skeletal muscle 17 Example: Glutamate receptors on neuron (dendritic spine)