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Intro to Cognitive Science Jamuna Subramaniam Department of Biological Sciences and Bioengineering Indian Institute of Technology Kanpur Higher order brain functions Language Learning and memory Thought Emotion Parts of the brain Diseases led to the discovery of the regions involved in specific functions. Brain imaging EEG collecting the peripheral brain electrical activity PET positron emission tomography – radioactive tracers in the water deutrium more active areas more blood flow increased radiotracer signal Individual neurotransmitters –radiotracers –receptor binding,occupancy and turnover molecular level studies possible at the systems level in humans. MRI&fMRIBased on bloodflow – paramagnetic property of hemoglobi Active brain regions oxygen bound blood flow will be higher. MRI Human brain The nervous system of a vertebrate Structure and functional areas of the cerebrum Brain regions involved in language Left lobe Wernicke’s area Auditory input understanding speech Broca’ s area Motor output Indelligible speech Areas active during different language tasks Language learning disability Dyslexia Molecular and cellular network level understanding !!!!!! NERVOUS SYSTEMS Three overlapping functions sensory input integration motor output Interconnected network of neurons Overview of a vertebrate nervous system • Networks of neurons with intricate connections form nervous systems Neuron Structure and Synapses. • The neuron is the structural and functional unit of the nervous system. • Nerve impulses are conducted along a neuron. • Dendrite → cell body → axon hillock → axon • Some axons are insulated by a myelin sheath. • Axon endings are called synaptic terminals. • They contain neurotransmitters which conduct a signal across a synapse. A synapse is the junction between a presynaptic and postsynaptic cell. Aplysia neuron • Types of Nerve Circuits. • Single presynaptic neuron → several postsynaptic neurons. • Several presynaptic neurons → single postsynaptic neuron. • Circular paths. Presynaptic neurons muscles – neuromuscular junctions Types of neurotransmission 1. Electrical 2. Chemical Every cell has a voltage, or membrane potential, across its plasma membrane • A membrane potential is a localized electrical gradient across the membrane. • Anions are more concentrated within a cell. • Cations are more concentrated in the extracellular fluid. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Measuring Membrane Potentials. Fig. 48.6a • An unstimulated cell usually have a resting potential of 70mV. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings How a Cell Maintains a Membrane Potential? • Cations • K+ is the principal intracellular cation. • Na+ is the principal extracellular cation. • Anions • Proteins, amino acids, sulfate, and phosphate are the principal intracellular anions. • Cl– is the principal extracellular anion. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings The basis of the membrane potential Fig. 48.7 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Types of gated ion channels • Chemicallygated ion channels open or close in response to a chemical stimulus. • Voltagegated ion channels open or close in response to a change in membrane potential. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Graded Potentials: Hyperpolarization and Depolarization • Graded potentials are changes in membrane potential Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Hyperpolarization • Gated K+ channels open → K+ diffuses out of the cell → the membrane potential becomes more negative. Fig. 48.8a Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Depolarization • Gated Na+ channels open → Na+ diffuses into the cell → the membrane potential becomes less negative. Fig. 48.8b Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings The Action Potential: All or Nothing Depolarization • If graded potentials sum to ≈ 55mV a threshold potential is achieved. • This triggers an action potential. • Axons only. Fig. 48.8c Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Step 1: Resting State. Fig. 48.9 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Step 2: Threshold. Fig. 48.9 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Step 3: Depolarization phase of the action potential. Fig. 48.9 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Step 4: Repolarizing phase of the action potential. Fig. 48.9 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Step 5: Undershoot. Fig. 48.9 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Propagation of the action potential Fig. 48.10 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Chemical or electrical communication between cells occurs at synapses • Electrical Synapses • Action potentials travel directly from the presynaptic to the postsynaptic cells via gap junctions. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Chemical Synapses • More common than electrical synapses. • Postsynaptic chemicallygated channels exist for ions such as Na+, K+, and Cl. • Depending on which gates open the postsynaptic neuron can depolarize or hyperpolarize. • Brought about by binding of neurotransmitters released from the presynaptic terminal to the postsynaptically localized chemicallygated channels Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fundamental currencies of the living cell DNA/RNA string of nucleotides nitrogenous base (four different bases pentose sugar and phosphate) Protein : string of amino acids (20 different amino acids) secondary, tertiary and quarternary structures DNA RNA Protein R NH2(CH)nCOOH Excitatory neurotransmission Positive event brings about membrane depolarization action potential generation – an action happening Major excitatory neurotransmitter in the CNS: glutamate Glutamate receptors : Ionotrophic (Na+ channel coupled) functional receptor complex is multimeric Three different types: Kainate, AMPA and NMDA receptors Diseases : conitnous firing excitotoxicity neuronal death in stroke, epilepsy Inhibitory neurotransmission Hyperpolarization – modulates – no action potential generation Inhibitory anion : Cl Inhibitory neurotransmitter : GABA gammaaminobutyric acid GABAA receptor complex pentameric – several types of subunits: alpha, beta, gamma, delta and rho – subunit subtypes. Have modulatory sites – anesthetics, antianxiety drugs In vitro patch clamp recording Nobel Price: Neher and Sakmann, 1991 The Major Known Neurotransmitters Integration of multiple synaptic inputs • Summation: graded potentials (EPSPs and IPSPs) are summed to either depolarize or hyperpolarize a postsynaptic neuron. Fig. 48.14 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Cellular communication at synapse Summation of input Action potential generation Output action Biological clock Emotions Learning and memory Human brain The Hypothalamus and Circadian Rhythms The biological clock is the internal timekeeper. • The clock’s rhythm usually does not exactly match environmental events. • Experiments in which humans have been deprived of external cues have shown that biological clock has a period of about 25 hours. • In mammals, the hypothalamic suprachiasmatic nuclei (SCN) function as a biological clock. • Produce proteins in response to light/dark cycles. • This, and other biological clocks, may be responsive to hormonal release, hunger, and various external stimuli. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings The limbic system (emotions) Learning and memory Shortterm memory stored in the frontal lobes. The establishment of longterm memory involves the hippocampus. The transfer of information from shortterm to longterm memory is enhanced by repetition (remember that when you are preparing for an exam). Influenced by emotional states mediated by the amygdala. Influenced by association with previously stored information. Synaptic signaling 1. Fast neurotransmission 2. Slow neurotransmission Signal transduction: Mode of regulation Phosphorylation dephosporylation Second messenger : cAMP, calcium, IP3, cGMP Figure 11.5 Overview of cell signaling (Layer 3) Overview of cell signaling (Layer 3) Figure 11.18 The specificity of cell signaling Cross talk between different signal cascades Signal amplification Learning and memory A Nobel laureate’s perspective Eric Kandel Selection of the problem: Learning and behavior easily tractable Selection of the organism: less complicated easy to observe behavior and molecular events Selection of behavior: Memory storage behavior Memory storage behavior Neural circuit Critical neurons Cellular and molecular changes in specific neurons Aplasia marine snail Modelbehavior Gill and siphon withdrawal upon tactile stimuli Aplasia neuron visible to naked eye Types of memory Short term: lasts only minutes Long term: lasts for days By practice (timed repetition) Short term memory Long term memory Behavior taught learned fear Sensitization shock in the tail, withdrawal of siphon and gill Neuronal circuit in gill withdrawal 24 mechanosensory neurons integrate siphon skin 6 monosynaptic connection to gill motor neuron Neurons in in vitro culture Injection of signal cascade components Molecular events Serotonin, dopamine Involvement of cAMP cascade Serotonin, dopamine cAMP levels Modulatory pathway involves cAMP cascade Sensory neurons release glutamate memory facilitation Synaptic plasticity Increase in strength. Increase in synapse number. Behavior : Spatial memory Hippocampal activation Diseases of Cognition Dementia – Loss of memory Alzheimer’s disease Cerebral cortex and hippocampus; Amyloid plague accumulation. Most prevalent – Complex neurodegenerative disease defects in the neurotransmitter acetylcholine and glutamate ! Huntington’s disease Diseases of the thought process Psychiatirc diseases • Schizophrenia • delusions, hallucinations • Too much of dopamine neurotransmitter signaling. Spinal cord injury THANK YOU