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Basis of Membrane Potential Membrane pumps: • use energy (ATP) to move ions against a concentration gradient • Na+-K+ pump moves K+ ions to the inside of the nerve cell – Expels 3 Na+ for every 2 K+ ions it brings in Ion Channel: • Channels are selective • Channels may be gated or un-gated • Gated channels are either voltage-gated or chemically-gated Sudden Changes in Ion Channels Generate Action Potentials • Action potential (AP) is a sudden and major change in membrane potential – Lasts 1-2 milliseconds – Pulse of electric charge is conducted along the axon at speeds up to 100 meters per second – Membrane potential changes from -60 to +50 mV Action Potential Movie 1 Role of voltage-gated ion channels in AP 1 1) Resting phase: Both sodium and potassium channels are closed, resting state maintained Role of voltage-gated ion channels in AP 2 2) Depolarizing phase: Acitvation gates of sodium channels open (letting in Na+) and potassium channels remain closed Role of voltage-gated ion channels in AP 3 3) Repolarizing phase: Inactivation gates close sodium channels and potassium channels open; potassium ions leave cell and lose + ions 2 Role of voltage-gated ion channels in AP 4 4) Undershoot: Both gates of sodium channels are closed but potassium channels remain open because of slower response. • Action potentials are conducted along axons without a reduction of signal • Na ions spread downstream, bringing next region to Na+ channel threshold Saltatory Conduction I • • • • Feature of vertebrate but not invertebrate axons Schwann cells have projections which wrap around axons AP appear to jump from node to node in myelinated axons Saltatory APs greatly accelerate rate of nerve impulse 3 Saltatory Conduction II • The speed of nerve impulse conduction also depends on diameter of axon -- larger diameters enable faster conduction • Unmyelinated axon responsible for squid escape behavior is whopping 1 mm in diameter Neurons, Synapses & Communication • Synapses are junctions where one cell influences another through the transfer of a chemical or electrical message • Chemical synapses: comprise most synapses in vertebrates • Electrical synapses: more abundant in invertebrates -- act rapidly but don’t integrate well Chemical Synapse Movie 4 Chemical Synapse • • • • • • AP depolarises membrane of synaptic terminal Triggers influx of Ca2+ Causes synaptic vesicles to fuse w/ membrane Release neurotransmitter molecules which bind to receptors of ion channels Binding of neurotransmitter molecules open ion channels Neurotransmitter is degraded rapidly, closing ion channel Neurotransmitters • Acetylcholine (Ach): one of most common neurotransmitters in vertebrates • Ach broken down by acetylcholinesterase • Breakdown products are then resynthesized into more Ach 5 Organization of the Vertebrate Nervous System Central Nervous System(CNS) – Brain: integration; complex behavior – Spinal cord: integrates simple (reflex responses) Peripheral Nervous System (PNS) • Sensory (afferent): – PNS --> CNS • Motor: (efferent) – CNS --> PNS – Somatic: signals to skeletal muscles in response to external stimuli (largely voluntary) – Autonomic: signals to skeletal muscles in response to internal stimuli (largely involuntary) Reflex Response 6 Autonomic Nervous System: Parasympathetic & Sympathetic Divisions • When parasympathetic (rest & digest) & sympathetic (flight or fight) divisions innervate same organ, effects are often antagonistic (opposite) • In general, parasympathetic division enhances activities that gain or conserve energy such as digestion & heart rate • In general, sympathetic division increases energy consumption & prepares individual for action by accelerating heart rate & metabolic rate Parts of the Human Brain • Hindbrain: controls movement & balance – Cerebellum – Pons – Medulla oblongata • Midbrain: conducts information & controls automatic activities essential for survival • Forebrain: – – – – Thalmus Hypothalmus Epithalmus Cerebrum: cerebral cortex, white matter, basal nuclei How Do We Determine Brain Function: The Tragic Case of Phineas P. Gage • 19th railroad construction accident blew tamping rod through brain of Phineas P. Gage • He survived w/ senses & memory in tact • Before accident, very responsible, well respected man • After accident, quarrelsome, bad tempered, lazy, profane and irresponsible 7 Alternatives to Ablation I: Electrodes Alternatives to Ablation II: Imaging Brain Function • • • Magnetic Resonance Imaging (MRI): exploits behavior of H atoms in water; useful at distinguishing soft tissue from bone Computed Tomography (CT): produces images in a series of thin Xray sections which can be integrated by a computer into 3D image Positron Emission Tomography (PET): can reveal local areas of physiological activity; involves use of minute quantities of radioisotopes injected into bloodstream Alternatives to ablation III: Reverse genetics • • • • DNA sequences (antisense expression constructs) can be injected into the brain and used to temporarily turn off specific genes Has been performed extensively in mice but only recently in primates (PNAS 2004) In rhesus monkeys, DNA antisense expression constructs were injected into the rhinal cortex in order block the D2 gene (produces dopamine receptors) In operant conditioning trials, the technique turned “slacker monkeys” into efficient, hardworkers by suppressing their ability to anticipate a reward 8 • Your Brain: – Use it or lose it! • Environmental complexity and diversity of social experience influence brain development in rats and mice Meditation alters brain structure • Brain imaging shows meditation increased thickness in cortical regions related to sensory, auditory and visual perception, as well as the automatic monitoring of heart rate or breathing, for example. • Most of the brain regions changed through meditation are in the right hemisphere, which is essential for sustaining attention (anger processed in left brain) PREFRONTAL CORTEX SYSTEM Functions • • • • • • • • • • • • • • • attention span perseverance planning judgment impulse control organization self-monitoring and supervision problem solving critical thinking forward thinking learning from experience and mistakes ability to feel and express emotions influences the limbic system empathy internal supervision 9 • • • • • • MRI scans compress 15 yr brain development (ages 5-20). Red indicates more gray matter, blue less gray matter. Gray matter wanes in a back to front wave as brain matures and neural connections are pruned. Areas performing more basic functions mature earlier; Areas for higher-order functions (emotion, self-control) mature later. The pre-frontal cortex, which handles reasoning and other "executive" functions, emerged late in evolution, and is among the last to mature. Frontal lobe injury – problems with: • • • • • • planning time persistence diligence inhibiting behavior distracted easily Prefrontal Cortex & Criminal Behavior • 41 murderers pleading NGRI and 41 controls. • Each group had 6 schizophrenics. (Raine et al. 1997) 10 Prefrontal Cortex & Criminal Behavior cont. • PET scans showed murderers had lower glucose metabolism in the bilateral and medial PFC • Reduced prefrontal activity has been observed to be associated with severe violence. The Brain, Emotions & Decision Making • • • Antonio Damasio: Looking for Spinosa Recognized importance of emotion in decision making from patients whose emotional centers had been damaged by strokes, accidents, or tumors. The change took place in the realm of day-to-day decision making, not in the realm of knowledge and skills. They could speak perfectly well. They could deal with the logic of a problem. They could learn new things.” Nonetheless, the lives of these tumor or stroke victims fell apart. Their marriages dissolved, and their careers were reduced to a series of odd jobs and disability checks. Transorbital Lobotomy • “Ice pick” Lobotomy about to be performed by Dr. Walter Freeman • Freeman believed that mental illness was related to overactive emotions, and that by cutting the brain he cut away these feelings. 11 The Essential Difference by Simon Baron-Cohen • • • • Male & female brains & the truth about autism Autism: A lifelong, neurological disorder appearing before the age of three yeas that involves language and communication deficits, and withdrawal from social contacts; pathological “self-absorption” Incidence of autism in males is more than 4 times higher than in females Baron-Cohen’s thesis: – the female brain is predominantly hard-wired for empathy – the male brain is predominantly hard-wired for understanding and building sysems – sex differences result from the effects of testosterone acting on brain development during fetal development – Autism: the extreme male brain Evolution of the human brain: comparative genomics • ASPM (Abnormal spindle-like microcephaly associated) gene shows an excess of nonsynonymous over synonymous substitutions in ape lineages leading to humans 12