Neurobiology BIO 475/675 Structure and function of the nervous system What is the brain, and how can we figure out how it works? Neurobiology BIO 475/675 A preview of neurobiology • Chapter 1 • Case study: the patellar reflex – the reflex – anatomy – neural signaling • the action potential – synaptic transmission • synapse • neurotransmitters: release and reception • Chapter 2 • Organization and evolution of nervous systems 1
Neurobiology BIO 475/675 Nervous system: basic function Outside Inside of body Light, sound, Sensory neuron smell, pressure, temperature, etc. Central Nervous System Higher level processing Motor (integration, coordination, neuron memory formation, physiological changes, etc.) ACTION! muscle Neurobiology BIO 475/675 The patellar reflex Fig 1.1 2
Neurobiology BIO 475/675 Anatomy of patellar reflex • Reflex loop – sensory terminal in muscle activated by stretch – Afferent signal: sent along sensory fiber into spinal cord – connection to motor neuron – Efferent signal: sent out of spinal cord along motor nerve fiber – nerve activates contraction of muscle Fig 1.2 Neurobiology BIO 475/675 Two-neuron reflex • Sensory neuron – stretch-activated fiber terminal in muscle – important for sensing contraction state of muscles, and for posture – cell body in dorsal root ganglion – terminal branches contact motor neurons • Motor neuron – cell body in spinal cord – extends fiber out to muscle 3
Neurobiology BIO 475/675 A neuron • A single motor neuron – embedded in matrix of other neurons and their fibers • Cell body – contains nucleus and other cell organelles • Two kinds of neurites – dendrites: input, highly branched – single axon: output – in case of motor neuron, axon extends out to contact muscle Neurobiology BIO 475/675 Signaling by neurons • Signal within a neuron: the action potential – electrical signal, spread by ionic changes in cell – efficiently transmitted along very long axons • Signal between neurons: the synapse – synapse is point of contact (tiny gap) between cells – specialized to promote and regulate transmission of signal from one cell to another – chemical signal is passed: neurotransmitter – neuron-muscle synapse = neuromuscular junction 4
Neurobiology BIO 475/675 Measuring the action potential • Insert voltage probe into sensory nerve fiber – microelectrode is a hollow glass tube – filled with saline solution – hooked up to voltage meter • The membrane potential – common to all cells – define: resting membrane potential • Stimulation causes Action Potential: – rapid depolarization, then quickly resets Neurobiology BIO 475/675 Behavior of the action potential • Transmits signal along the nerve fiber • Neuron fires • First fires at terminal, then signal is propagated along fiber – evidence for propagation • Speed: 50+ meters per sec – So, what time from toe to spinal cord, and back to toe? • What questions does this raise? 5
Neurobiology BIO 475/675 Synaptic transmission Action potential Action potential Postsynaptic Presynaptic terminal terminal Synapse • Presynaptic terminal: vesicles store neurotransmitter • Action potential depolarizes presynaptic terminal – triggers fusion of synaptic vesicles to membrane; release of neurotransmitter • Neurotransmitter binds to receptors on postsynaptic membrane • Receptors depolarize postsynaptic terminal • Action potential carries signal to new target cells Neurobiology BIO 475/675 Synaptic transmission Action potential Action potential Postsynaptic Presynaptic terminal terminal Synapse Electrical Chemical Electrical • Important point of regulation – Electrical signal is all-or-none – But chemical signal can be modulated • Pharmacology: drugs modify synaptic transmission – increase or decrease transmission of signals between neurons 6
Neurobiology BIO 475/675 Acetylcholine, ACh • Several lines of evidence: motor neurons use acetylcholine as a neurotransmitter • Synthetic enzyme: choline acetyltransferase • Degradative enzyme: acetylcholine esterase Neurobiology BIO 475/675 Evidence for neurotransmitter • How can we determine if a neurotransmitter is used in a particular neural pathway? • Identify presence of synthetic enzyme Fig 1.8 • Technique: antibody labeling – immunocytochemistry – immunofluorescence • Isolate antibody molecule that specifically binds to choline acetyltransferase protein – cut sections of brain – wash with solution of antibody – visualize with color reaction: Fig 1.8 • Neurons of a type are often clustered together – termed “nucleus” 7
Neurobiology BIO 475/675 Neurotransmitter degradation • Neurotransmitter signal needs to be short, so… • Neurotransmitters need to be broken down quickly – several different mechanisms for this • Degradative enzyme: acetylcholine esterase – AChE, or Achase • AChE is present in neuromuscular junction Fluorescent label of motor axon terminal Pattern of AChE enzyme activity Neurobiology BIO 475/675 Neurotransmitter degradation • Neurotransmitters need to be broken down quickly • Genetic defect leads to paralysis in humans • Congenital endplate acetylcholine esterase deficiency – failure to produce functional AChE at neuromuscular junction – ACh released, but not broken down – So, one signal from motor neurons, but multiple muscle contractions 8
Neurobiology BIO 475/675 What senses neurotransmitter? • Acetylcholine receptor: – AChR, Fig 1.10 • Membrane structure: – ions cannot cross membrane • ACh receptor: AChR – ligand-gated ion channel – ACh diffuses to postsynaptic membrane – ACh binds, channel opens, lets positive ions cross membrane – depolarizes postsynaptic cell membrane • Triggers action potential in muscle fiber, leads to muscle contraction • AChR present in synapse: – fluorescent-tagged molecule that binds to AChR – alpha bungarotoxin, from snake venom Neurobiology BIO 475/675 Synaptic transmission Action potential Action potential Postsynaptic Presynaptic terminal terminal Synapse • Presynaptic terminal: vesicles store neurotransmitter • Action potential depolarizes presynaptic terminal – triggers fusion of synaptic vesicles to membrane; release of neurotransmitter • Neurotransmitter binds to receptors on postsynaptic membrane • Receptors depolarize postsynaptic terminal • Action potential carries signal to new target cells 9
Neurobiology BIO 475/675 Anatomy of patellar reflex • Fig 1.2 Neurobiology BIO 475/675 Systems neurobiology • Neurons are part of larger neural circuits or systems • Example: patellar reflex can be consciously repressed • How are groups of neurons organized into larger functional circuits? • Types of neurons: – sensory, motor, interneurons 10
Neurobiology BIO 475/675 Organization of nervous systems • Evolution of nervous systems – electrical signaling important for single cells – nerve nets – bilateral symmetry • central nervous system evolved – central vs. peripheral • neurons became more specialized • cephalization – head nervous system bigger, more complex, more interneurons Neurobiology BIO 475/675 Hierarchical organization of NS • Head – primary responsibility to initiate action – integration of sensory information – coordination of motor • Vertebrates – have specialized brain that regulates spinal cord • chicken • Brain subdivisions – forebrain – midbrain – hindbrain – spinal cord 11
Neurobiology BIO 475/675 Brain subdivisions • Various brain regions become specialized in different vertebrates • Rodents: nocturnal mammals – relatively large olfactory bulbs – primary reception and processing of olfactory signals • Humans – Forebrain, specifically cerebral cortex, is hugely expanded – complex folds allow very large surface area – increased number of neurons Neurobiology BIO 475/675 Brain subdivisions • Make table of main subdivisions and functions 12
Neurobiology BIO 475/675 Overall human CNS anatomy Fig 2.5 Neurobiology BIO 475/675 A preview of neurobiology • Chapter 1 • Case study: the patellar reflex – the reflex – anatomy – neural signaling • the action potential – synaptic transmission • synapse • neurotransmitters: release and reception • Chapter 2 • Organization and evolution of nervous systems 13
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