Unit HUMAN PHYSIOLOGY 1

HUMAN PHYSIOLOGY - MOD. 1

Code	A000329
CFU	5
Learning activities	Base
Area	Funzioni biologiche integrate di organi, sistemi e apparati umani
Academic discipline	BIO/09
Type of study-unit	Obbligatorio (Required)

Cognomi A-L

CFU

5

Teacher

Fabio Massimo Botti

Teachers

• Fabio Massimo Botti

Hours

• 62.5 ore - Fabio Massimo Botti

Language of instruction

Italian

Contents

Sensory system
Motor system
Higher functions

Reference texts

Fisiologia medica - F. Conti Edi Ermes
Kandel, Schwartz, Jessel - Principi di Neuroscienze ed. Casa Editrice Ambrosiana - III edizione italiana
Schmidt- Thews-Lang Fisiologia umana Idelson-Gnocchi

Educational objectives

Knowledge of the physiology of the nervous system

Prerequisites

In order to understand the contents of the course and to achieve the learning objectives, the student must possess the fundamental knowledge in:
Physics
Chemistry
Biochemistry
Human anatomy

Teaching methods

theoretical and theoretical-practical frontal lessons

Other information

-

Learning verification modality

The level of learning achieved will be evaluated with a final oral exam consisting of two tests, which the student can take at different times. A test is aimed at ascertaining the level of knowledge reached on the theoretical contents indicated in the program related to organ physiology (cardio-circulatory, respiratory, urinary and digestive systems) and the other on the contents related to the physiology of the nervous and endocrine system. In each test the student will be asked two questions by two different teachers of the course. The test is considered to be passed if the student reaches the sufficiency in both questions. The sequence of tests is chosen by the student. The oral exam will also allow the student to verify the communication skills of the student with language properties and the organization of the exposition on the topics under discussion and his reasoning skills.
The final grade will be the average of the marks obtained in the 4 questions.

For information on support services for students with disabilities and / or DSA visit the page http://www.unipg.it/disabilita-e-dsa

Extended program

Physiology of muscle contraction
•. Striated muscle: types of contraction, length / strength curve, load / speed curve. Types of muscle fibers, motor units, single twitch and muscle tetanus, force modulation. Electromyography
Sensory systems.
• Organization of the sensitive system. Receptor concept, sensory modalities, receptor classification, receptor potential, intensity coding, adaptation, receptive fields, lateral inhibition. Psychophysics of perception.
• Vision. Eye: functional anatomy, photoreceptors and photo-transduction, retinal network, ganglion cells and optic nerve. Central visual pathways decussation, SNA contingents, superior colliculus, lateral geniculate body. Cortical processing: primary visual cortex (V1), receptive fields and columnar organization. Dorsal and ventral cortical pathways.
• Hearing. Ear: functional anatomy, cochlea and Corti organ, transduction mechanism, active amplification mechanisms and lateral inhibition. Acoustic pathways: tonotopic organization, ganglionic connections, spatial localization, auditory cortices.
• Vestibular receptors. Semicircular canals: structure, transduction mechanism. Utricolo and sacculo: structure, transduction mechanism. Central connections.
• Touch sense. Types of receptors and their characteristics, discrimination, metameric organization, ascending pathways, somatotopic organization.
• Proprioception. Neuromuscular spindles: structure, transduction mechanism, innervation, role of gamma innervation. Golgi -tendon organs: localization, transduction mechanism. Ascending pathways.
• Thermal sensitivity. Caloceptors, frigoceptors, ascending pathways.
• Pain. Types of pain, receptors, afferent pathways, referred pain, hyperalgesia, ascending pathways, peripheral and central control mechanisms.
Motor system and higher functions.
• Spinal cord and reflexes. Morpho-functional characteristics, basic circuits, reflex concept, modulation, deep reflexes (myotatic), superficial reflexes (flexor r.).
• Locomotion. Phillipson model, kinematics, central pattern generator, integration of afferent signals, supraspinal control.
• Posture and Balance. Postural tone, vestibular, reticular and cerebellar contributions, postural stability, visual and somatosensory contributions, integration, postural reactions, postural strategies and synergies.
• Voluntary movement. Organization of descending pathways, primary motor area, premotor areas, supplementary motor areas, reaching and grasping, mirror neurons.
• Basal ganglia, basic circuitry, direct and indirect pathways, hypo and hyperkinetic disorders, motor, oculomotor, cognitive, and limbic circuits.
• Cerebellum. G eneral organization, basic circuit, simple and complex potentials, recalibration, Typical signs of cerebellar pathology
• Eye movements. Types of eye movements, extrinsic muscles. Vestibulo-ocular reflex: control network, transfer function, time constants and central integrator. Optokinetic reflex: characteristics of the response, integration with the vestibulo-ocular reflex. Saccadic eye movements: control circuits, role of the superior colliculus, frontal eye fields. Smooth pursuit eye movements.
• Electroencephalography (EEG), sleep and consciousness. Source of EEG signal, EEG rhythms, synchronization, evoked potentials. Sleep: sleep stages,regulation of the sleep-wake cycle, circadian rhythms. Definition of consciousness, integrated information theory.
• Language and lateralization. Areas involved in languageand aphasia. Written language and spoken language. Anatomical asymmetries, studies on split brain, hemispheric specialization.
• Memory and learning. Classification criteria of types of memory. Non-associative memory (habituation and sensitization) experimental models. Associative memory, classical and operative conditioning. explicit memory implicit memory types, hippocampal role, place cells and spatial memory
Vegetative controls. • Autonomic nervous system. Structure, similarities and differences of the sympathetic and parasympathetic sections, neurotransmitters and receptors. •Hypothalamus. Functions: endocrine regulation, thermoregulation, nutrition regulation, emotional expression. • Basal metabolism. Concept of basal metabolic rate, energy balance, basal conditions, direct calorimetry and indirect calorimetry. • Thermoregulation. Central and peripheral temperature, heat exchange mechanisms, thermal neutral zone, responses to cold, responses to heat, fever. •Features of the endocrine system. Functions controlled by hormones, chemical nature, biosynthesis, transduction mechanisms, secretion control. • Growth hormone. Control of secretion, IGF, direct and indirect effects, interaction with other hormones, dwarfism and gigantism.•Thyroid hormones. Biosynthesis, secretion control, effects on metabolism and growth, thyroid pathologies. •Integrated blood sugar control. Insulin: biosynthesis, secretion control, metabolic effects on different target tissues, effect on growth. Glucagon: control of secretion, metabolic effects in various tissues, synergism with other hyperglycaemic hormones. •Integrated blood calcium control. Plasma calcium, calcium and phosphate balance, calcium absorption and reabsorption, bone metabolism, parathyroid hormone, calcitriol and calcitonin. •Integrated response to stress. Definition of stress, phases according to Selye, nervous arm and chemical arm. Adrenaline: biosynthesis, adrenergic receptors, metabolic effects. Cortisol: secretion control, metabolic effects, other effects.

Cognomi M-Z

CFU

5

Teacher

Fabio Massimo Botti

Teachers

• Fabio Massimo Botti

Hours

• 62.5 ore - Fabio Massimo Botti

Language of instruction

Italian

Contents

Sensory system
Motor system
Higher functions

Reference texts

Fisiologia medica - F. Conti Edi Ermes
Kandel, Schwartz, Jessel - Principi di Neuroscienze ed. Casa Editrice Ambrosiana - III edizione italiana
Schmidt- Thews-Lang Fisiologia umana Idelson-Gnocchi

Educational objectives

Knowledge of the physiology of the nervous system

Prerequisites

In order to understand the contents of the course and to achieve the learning objectives, the student must possess the fundamental knowledge in:
Physics
Chemistry
Biochemistry
Human anatomy

Teaching methods

theoretical and theoretical-practical frontal lessons

Other information

-

Learning verification modality

The level of learning achieved will be evaluated with a final oral exam consisting of two tests, which the student can take at different times. A test is aimed at ascertaining the level of knowledge reached on the theoretical contents indicated in the program related to organ physiology (cardio-circulatory, respiratory, urinary and digestive systems) and the other on the contents related to the physiology of the nervous and endocrine system. In each test the student will be asked two questions by two different teachers of the course. The test is considered to be passed if the student reaches the sufficiency in both questions. The sequence of tests is chosen by the student. The oral exam will also allow the student to verify the communication skills of the student with language properties and the organization of the exposition on the topics under discussion and his reasoning skills.
The final grade will be the average of the marks obtained in the 4 questions.

For information on support services for students with disabilities and / or DSA visit the page http://www.unipg.it/disabilita-e-dsa

Extended program

Physiology of muscle contraction
•. Striated muscle: types of contraction, length / strength curve, load / speed curve. Types of muscle fibers, motor units, single twitch and muscle tetanus, force modulation. Electromyography
Sensory systems.
• Organization of the sensitive system. Receptor concept, sensory modalities, receptor classification, receptor potential, intensity coding, adaptation, receptive fields, lateral inhibition. Psychophysics of perception.
• Vision. Eye: functional anatomy, photoreceptors and photo-transduction, retinal network, ganglion cells and optic nerve. Central visual pathways decussation, SNA contingents, superior colliculus, lateral geniculate body. Cortical processing: primary visual cortex (V1), receptive fields and columnar organization. Dorsal and ventral cortical pathways.
• Hearing. Ear: functional anatomy, cochlea and Corti organ, transduction mechanism, active amplification mechanisms and lateral inhibition. Acoustic pathways: tonotopic organization, ganglionic connections, spatial localization, auditory cortices.
• Vestibular receptors. Semicircular canals: structure, transduction mechanism. Utricolo and sacculo: structure, transduction mechanism. Central connections.
• Touch sense. Types of receptors and their characteristics, discrimination, metameric organization, ascending pathways, somatotopic organization.
• Proprioception. Neuromuscular spindles: structure, transduction mechanism, innervation, role of gamma innervation. Golgi -tendon organs: localization, transduction mechanism. Ascending pathways.
• Thermal sensitivity. Caloceptors, frigoceptors, ascending pathways.
• Pain. Types of pain, receptors, afferent pathways, referred pain, hyperalgesia, ascending pathways, peripheral and central control mechanisms.
Motor system and higher functions.
• Spinal cord and reflexes. Morpho-functional characteristics, basic circuits, reflex concept, modulation, deep reflexes (myotatic), superficial reflexes (flexor r.).
• Locomotion. Phillipson model, kinematics, central pattern generator, integration of afferent signals, supraspinal control.
• Posture and Balance. Postural tone, vestibular, reticular and cerebellar contributions, postural stability, visual and somatosensory contributions, integration, postural reactions, postural strategies and synergies.
• Voluntary movement. Organization of descending pathways, primary motor area, premotor areas, supplementary motor areas, reaching and grasping, mirror neurons.
• Basal ganglia, basic circuitry, direct and indirect pathways, hypo and hyperkinetic disorders, motor, oculomotor, cognitive, and limbic circuits.
• Cerebellum. G eneral organization, basic circuit, simple and complex potentials, recalibration, Typical signs of cerebellar pathology
• Eye movements. Types of eye movements, extrinsic muscles. Vestibulo-ocular reflex: control network, transfer function, time constants and central integrator. Optokinetic reflex: characteristics of the response, integration with the vestibulo-ocular reflex. Saccadic eye movements: control circuits, role of the superior colliculus, frontal eye fields. Smooth pursuit eye movements.
• Electroencephalography (EEG), sleep and consciousness. Source of EEG signal, EEG rhythms, synchronization, evoked potentials. Sleep: sleep stages,regulation of the sleep-wake cycle, circadian rhythms. Definition of consciousness, integrated information theory.
• Language and lateralization. Areas involved in languageand aphasia. Written language and spoken language. Anatomical asymmetries, studies on split brain, hemispheric specialization.
• Memory and learning. Classification criteria of types of memory. Non-associative memory (habituation and sensitization) experimental models. Associative memory, classical and operative conditioning. explicit memory implicit memory types, hippocampal role, place cells and spatial memory
Vegetative controls. • Autonomic nervous system. Structure, similarities and differences of the sympathetic and parasympathetic sections, neurotransmitters and receptors. •Hypothalamus. Functions: endocrine regulation, thermoregulation, nutrition regulation, emotional expression. • Basal metabolism. Concept of basal metabolic rate, energy balance, basal conditions, direct calorimetry and indirect calorimetry. • Thermoregulation. Central and peripheral temperature, heat exchange mechanisms, thermal neutral zone, responses to cold, responses to heat, fever. •Features of the endocrine system. Functions controlled by hormones, chemical nature, biosynthesis, transduction mechanisms, secretion control. • Growth hormone. Control of secretion, IGF, direct and indirect effects, interaction with other hormones, dwarfism and gigantism.•Thyroid hormones. Biosynthesis, secretion control, effects on metabolism and growth, thyroid pathologies. •Integrated blood sugar control. Insulin: biosynthesis, secretion control, metabolic effects on different target tissues, effect on growth. Glucagon: control of secretion, metabolic effects in various tissues, synergism with other hyperglycaemic hormones. •Integrated blood calcium control. Plasma calcium, calcium and phosphate balance, calcium absorption and reabsorption, bone metabolism, parathyroid hormone, calcitriol and calcitonin. •Integrated response to stress. Definition of stress, phases according to Selye, nervous arm and chemical arm. Adrenaline: biosynthesis, adrenergic receptors, metabolic effects. Cortisol: secretion control, metabolic effects, other effects.

HUMAN PHYSIOLOGY - MOD. 2

Code	A000331
CFU	5
Teacher	Alessandro Tozzi
Learning activities	Base
Area	Funzioni biologiche integrate di organi, sistemi e apparati umani
Academic discipline	BIO/09
Type of study-unit	Obbligatorio (Required)

Cognomi A-L

CFU

5

Teacher

Alessandro Tozzi

Teachers

• Alessandro Tozzi

Hours

• 62.5 ore - Alessandro Tozzi

Language of instruction

Italian

Reference texts

Fisiologia medica - F. Conti Edi Ermes
Kandel, Schwartz, Jessel - Principi di Neuroscienze ed. Casa Editrice Ambrosiana - III edizione italiana

Educational objectives

Knowledge of the physiology of the nervous system.

Prerequisites

The student in order to understand the content covered in the teaching of Human Physiology and achieve the intended learning objectives must possess the fundamental knowledge derived from the previous teachings and in particular of:
Physics
Chemistry
Biochemistry
Human Anatomy.

Teaching methods

Frontal lessons.

Learning verification modality

The level of learning achieved will be assessed by final oral examination consisting of two tests, which the student may take at different times. One test is designed to ascertain the level of knowledge attained on the theoretical contents indicated in the syllabus related to Organ Physiology (cardio-circulatory, respiratory, urinary and digestive systems) and the other on the contents related to the Physiology of the Nervous and Endocrine Systems. In each test the student will be asked two questions by two different lecturers of the course. The test is considered passed if the student achieves a passing grade in both questions. The sequence of the tests is the student's choice. The oral examination will also test the student's ability to communicate with properties of language and organization of exposition on the topics under discussion and his or her ability to reason.
The final grade will result from the average of the marks obtained in the 4 questions.

For information on support services for students with disabilities and/or DSA visit http://www.unipg.it/disabilita-e-dsa

Extended program

Nervous system.
-Internal medium. Intra- and extracellular fluid. Homeostasis. Negative feedback homeostatic mechanisms. Positive feedback and anticipatory controls in feedforward. Movement of molecules in the body: volume flow and flow by diffusion. Cellular communication systems. General organization of the nervous system: afferent, central, efferent systems.
-Diffusion. The neuronal membrane, proteins and transporters. Fick's equation. Diffusion coefficient. Permeability. Carrier-mediated passage. Facilitated diffusion and active transport. Saturation. Transport. Main mechanisms of facilitated transport. Main primary and secondary active transport systems.
-Ion channels. Simple diffusion through ion channels. Protein structure of the channel. Passive and variable access channels. Selectivity. Opening/closing gate and inactivation. Mechanisms of opening: ligand, potential, phosphorylation, mechanical stretching. Mechanism of voltage-dependence. Blocking and inactivation. The patch-clamp technique for single channel or total current measurements. Ohm's law. Ohmic and rectifying channels. The neuron as a coaxial conductor. Recording of membrane potentials of a neuron. Intracellular recording: description of resting potential, hyperpolarization, depolarization, action potential. Main voltage-dependent channels.
-Membrane potential. Concentration difference and membrane permeability. Simplified model of the genesis of membrane potential. Equilibrium potential for an ion: Nernst equation. Goldman equation. Sodium/potassium pump: maintenance of intracellular concentrations and electrogenic effect. Potassium and sodium permeability of the resting membrane. Contribution of the sodium-potassium pump.
-Action potential: changes in membrane permeability during the rising and falling phases of the sodium, potassium action potential. Effects of electric current on the membrane. Polarity: depolarization and hyperpolarization. Intensity: correlation of stimulus intensity with amplitude of potential change. Threshold level for the emergence of action potential. Law of all or nothing. Ionic bases. Refractory period: absolute and relative. Ionic mechanisms of the refractory period.
-Conduction of electrical signals along excitable membranes. Passive or electrotonic conduction. Local currents or electrotonic currents: time course and spatial distribution of potential. Time constant and space constant. Conduction of action potential. Spatial distribution of potential in an axon. Influence of axon diameter on space constant. Relationship between space constant and membrane resistance/axon internal resistance ratio. Propagation of action potential: stimulation above threshold and recording along the fiber. Space constant and speed of action potential propagation. Jumping conduction. Correlation between conduction velocity and distance between nodes. Classifications of nerve fibers according to diameter and conduction velocity.
-Chemical synapses: transmission and reception phase. Ionotropic and metabotropic postsynaptic receptors. Excitatory and inhibitory graded postsynaptic potentials. Description of the neuro-muscle synapse. Plaque potentials. Recording of miniature plaque potentials and their disappearance after motor neuron destruction. Concept of "quantum" of neurotransmitter. Mechanisms of synaptic transmission in the neuro-muscle synapse; active zones. Miniature plaque potentials: demonstration of the quantal nature of acetylcholine release. Relationships with number of acetylcholine molecules in a quantum and synaptic vesicles. Number of vesicles released. Effects of cytopathic calcium on neurotransmitter release. Opening of calcium channels with gate potential and entry of calcium into the terminal. Calcium channel opening threshold and low opening rate. Effect of calcium on release probability.
-Neurotransmitter exocytosis. Synaptic vesicle cycle: docking mobilization and priming. Regulatory proteins: synapsin, synaptotagmin, SNARE complex, alpha-synuclein.
-Turn-over of acetylcholine. Diffusion, inactivation by acetylcholinesterase, binding to synaptic receptors. Reuptake of choline. Action of curare on muscle receptors. Ionic selectivity of muscle nicotinic acetylcholine receptor: reversal potential of plaque potential and single channel current.
-Central chemical synapses. Excitatory fibers and inhibitory interneuron. Excitatory and inhibitory postsynaptic potentials and respective ionic mechanisms. Passive propagation of postsynaptic potentials. Spatial and temporal summation. Presynaptic inhibition and possible mechanisms. Presynaptic facilitation and role of calcium-permeable presynaptic nicotinic receptors.
-Chemical neurotransmitters. Definition and classification. Classical neurotransmitters and neuropeptides. Major neurotransmitters: acetylcholine, glutamate, gamma-amino-butyric acid (GABA), glycine, dopamine, norepinephrine, serotonin. Retrograde messengers. Dale-Eccles principle.
-Synaptic receptors. Principles of neurotransmitter action: physiological properties of ionotropic and G-protein-coupled receptors. Possible cellular effects of G proteins. Receptor desensitization. Synaptic facilitation, short-term synaptic depression, post-tetanic potentiation. Glutamate receptors: AMPA, kainate, NMDA, metabotropic. GABA and glycine receptors. Cholinergic, dopaminergic, noradrenergic and serotonergic projection systems.
-Synaptic plasticity. Synaptogenesis and synaptic remodeling. Short- and long-term functional synaptic plasticity phenomena. Synaptic facilitation and post-tetanic potentiation. Long-term phenomena: long-term potentiation and depression of synaptic transmission; glutamatergic synapse, pre- and post-synaptic organization of receptors, enzymes and structural elements; role of NMDA receptor. LTP and LTD: early and late phases; pre- and post-synaptic modifications; phosphorylations, defosphorylations, retrograde messengers and structural remodeling. Modulation of signaling pathways in long-term plasticity and role of neurotrophins.
-Autonomic nervous system. Functions. Structure, similarities and differences of sympathetic and parasympathetic sections. Pre- and postganglionic neurons. Neurotransmitters and receptors. The hypothalamus and vegetative control mechanisms.
-Sensory system.
-Receptors. Classification. Receptor and generator potential. -Transduction. Amplitude and frequency coding. Threshold. Stimulus intensity/amplitude relationship of receptor potential and frequency of action potentials. Receptor threshold. Stevens' law. Receptors with exponent less than, equal to and greater than 1. Saturation. Adaptation: tonicity and phasicity. Modality of sensation. Appropriate stimulus. Receptor potential or generating potential.
-Somatic sensibility. Tactile sensitivity: tonic and phasic receptors, absolute threshold simultaneous spatial threshold. Lateral inhibition. Central pathways. Morphognosy, ilognosy, stereognosy. Vibration. Tickle.
Thermal sensitivity. Caloreceptors, frigoreceptors. Central pathways. Psychophysics of thermal sensation.
Pain sensitivity. Classification of receptors. Types of pain. Affirmatory system. Specificity of pain signal and mechanisms of stimulation. Wide dynamic spectrum neurons (allodynia) and specific neurons. Neurotransmitters and neuromodulators of pain. Sensitive tissues. Referred pain. Input and descending control of pain.
Proprioctivity. Mechanisms of receptor activation. Primary and secondary afferents of the neuromuscular spindle. Static and dynamic gamma innervation. Golgi muscle-tendon organ. Sensitivity to changes in length, velocity and force. Proprioceptive reflexes.
Skeletal and smooth muscle.
-Skeletal muscle. Ultrastructure of skeletal muscle. Organization into myofibrils and sarcomeres. Association of contractile and regulatory proteins. Contractile mechanism, interaction of cross bridges with thin filaments. Calcium and troponin.
-Electromechanical coupling. Function of T-tubules, receptors for dihydropyridine, ryanodine. Mechanisms of sarcoplasmic calcium recovery: ATP-dependent calcium pump, Ca2+/Na+ exchanger.
-Simple muscle shock. Shock summation and muscle tetanus. Role of ATP and energy supply.
-Biophysics of the contractile system. Muscle tension and loading. Isometric and isotonic contraction. Force, Length, Speed, Power. Tension-length relationship. Active, passive and total tension. Force-velocity relationship. Mechanical power.
-Motor units. Muscle fibers and motor units FF, FR, S, muscle fatigue, order of recruitment. Force control: recruitment and frequency (Renshaw's Inhibition).
-Smooth muscle. Unit and multi-unit smooth muscle. Function. Factors stimulating contraction. Smooth muscle action potential, hormonal, paracrine and stretch factors. Slow waves, myogenic tone. Pace-maker potentials. Electro-mechanical coupling. Transverse bridge cycle. Phasic and tonic contraction. Length-tension relationship, velocity force curve.

Cognomi M-Z

CFU

5

Teacher

Alessandro Tozzi

Teachers

• Alessandro Tozzi

Hours

• 62.5 ore - Alessandro Tozzi

Language of instruction

Italian

Reference texts

Fisiologia medica - F. Conti Edi Ermes
Kandel, Schwartz, Jessel - Principi di Neuroscienze ed. Casa Editrice Ambrosiana - III edizione italiana

Educational objectives

Knowledge of the physiology of the nervous system.

Prerequisites

The student in order to understand the content covered in the teaching of Human Physiology and achieve the intended learning objectives must possess the fundamental knowledge derived from the previous teachings and in particular of:
Physics
Chemistry
Biochemistry
Human Anatomy.

Teaching methods

Frontal lessons.

Learning verification modality

The level of learning achieved will be assessed by final oral examination consisting of two tests, which the student may take at different times. One test is designed to ascertain the level of knowledge attained on the theoretical contents indicated in the syllabus related to Organ Physiology (cardio-circulatory, respiratory, urinary and digestive systems) and the other on the contents related to the Physiology of the Nervous and Endocrine Systems. In each test the student will be asked two questions by two different lecturers of the course. The test is considered passed if the student achieves a passing grade in both questions. The sequence of the tests is the student's choice. The oral examination will also test the student's ability to communicate with properties of language and organization of exposition on the topics under discussion and his or her ability to reason.
The final grade will result from the average of the marks obtained in the 4 questions.

For information on support services for students with disabilities and/or DSA visit http://www.unipg.it/disabilita-e-dsa

Extended program

Nervous system.
-Internal medium. Intra- and extracellular fluid. Homeostasis. Negative feedback homeostatic mechanisms. Positive feedback and anticipatory controls in feedforward. Movement of molecules in the body: volume flow and flow by diffusion. Cellular communication systems. General organization of the nervous system: afferent, central, efferent systems.
-Diffusion. The neuronal membrane, proteins and transporters. Fick's equation. Diffusion coefficient. Permeability. Carrier-mediated passage. Facilitated diffusion and active transport. Saturation. Transport. Main mechanisms of facilitated transport. Main primary and secondary active transport systems.
-Ion channels. Simple diffusion through ion channels. Protein structure of the channel. Passive and variable access channels. Selectivity. Opening/closing gate and inactivation. Mechanisms of opening: ligand, potential, phosphorylation, mechanical stretching. Mechanism of voltage-dependence. Blocking and inactivation. The patch-clamp technique for single channel or total current measurements. Ohm's law. Ohmic and rectifying channels. The neuron as a coaxial conductor. Recording of membrane potentials of a neuron. Intracellular recording: description of resting potential, hyperpolarization, depolarization, action potential. Main voltage-dependent channels.
-Membrane potential. Concentration difference and membrane permeability. Simplified model of the genesis of membrane potential. Equilibrium potential for an ion: Nernst equation. Goldman equation. Sodium/potassium pump: maintenance of intracellular concentrations and electrogenic effect. Potassium and sodium permeability of the resting membrane. Contribution of the sodium-potassium pump.
-Action potential: changes in membrane permeability during the rising and falling phases of the sodium, potassium action potential. Effects of electric current on the membrane. Polarity: depolarization and hyperpolarization. Intensity: correlation of stimulus intensity with amplitude of potential change. Threshold level for the emergence of action potential. Law of all or nothing. Ionic bases. Refractory period: absolute and relative. Ionic mechanisms of the refractory period.
-Conduction of electrical signals along excitable membranes. Passive or electrotonic conduction. Local currents or electrotonic currents: time course and spatial distribution of potential. Time constant and space constant. Conduction of action potential. Spatial distribution of potential in an axon. Influence of axon diameter on space constant. Relationship between space constant and membrane resistance/axon internal resistance ratio. Propagation of action potential: stimulation above threshold and recording along the fiber. Space constant and speed of action potential propagation. Jumping conduction. Correlation between conduction velocity and distance between nodes. Classifications of nerve fibers according to diameter and conduction velocity.
-Chemical synapses: transmission and reception phase. Ionotropic and metabotropic postsynaptic receptors. Excitatory and inhibitory graded postsynaptic potentials. Description of the neuro-muscle synapse. Plaque potentials. Recording of miniature plaque potentials and their disappearance after motor neuron destruction. Concept of "quantum" of neurotransmitter. Mechanisms of synaptic transmission in the neuro-muscle synapse; active zones. Miniature plaque potentials: demonstration of the quantal nature of acetylcholine release. Relationships with number of acetylcholine molecules in a quantum and synaptic vesicles. Number of vesicles released. Effects of cytopathic calcium on neurotransmitter release. Opening of calcium channels with gate potential and entry of calcium into the terminal. Calcium channel opening threshold and low opening rate. Effect of calcium on release probability.
-Neurotransmitter exocytosis. Synaptic vesicle cycle: docking mobilization and priming. Regulatory proteins: synapsin, synaptotagmin, SNARE complex, alpha-synuclein.
-Turn-over of acetylcholine. Diffusion, inactivation by acetylcholinesterase, binding to synaptic receptors. Reuptake of choline. Action of curare on muscle receptors. Ionic selectivity of muscle nicotinic acetylcholine receptor: reversal potential of plaque potential and single channel current.
-Central chemical synapses. Excitatory fibers and inhibitory interneuron. Excitatory and inhibitory postsynaptic potentials and respective ionic mechanisms. Passive propagation of postsynaptic potentials. Spatial and temporal summation. Presynaptic inhibition and possible mechanisms. Presynaptic facilitation and role of calcium-permeable presynaptic nicotinic receptors.
-Chemical neurotransmitters. Definition and classification. Classical neurotransmitters and neuropeptides. Major neurotransmitters: acetylcholine, glutamate, gamma-amino-butyric acid (GABA), glycine, dopamine, norepinephrine, serotonin. Retrograde messengers. Dale-Eccles principle.
-Synaptic receptors. Principles of neurotransmitter action: physiological properties of ionotropic and G-protein-coupled receptors. Possible cellular effects of G proteins. Receptor desensitization. Synaptic facilitation, short-term synaptic depression, post-tetanic potentiation. Glutamate receptors: AMPA, kainate, NMDA, metabotropic. GABA and glycine receptors. Cholinergic, dopaminergic, noradrenergic and serotonergic projection systems.
-Synaptic plasticity. Synaptogenesis and synaptic remodeling. Short- and long-term functional synaptic plasticity phenomena. Synaptic facilitation and post-tetanic potentiation. Long-term phenomena: long-term potentiation and depression of synaptic transmission; glutamatergic synapse, pre- and post-synaptic organization of receptors, enzymes and structural elements; role of NMDA receptor. LTP and LTD: early and late phases; pre- and post-synaptic modifications; phosphorylations, defosphorylations, retrograde messengers and structural remodeling. Modulation of signaling pathways in long-term plasticity and role of neurotrophins.
-Autonomic nervous system. Functions. Structure, similarities and differences of sympathetic and parasympathetic sections. Pre- and postganglionic neurons. Neurotransmitters and receptors. The hypothalamus and vegetative control mechanisms.
-Sensory system.
-Receptors. Classification. Receptor and generator potential. -Transduction. Amplitude and frequency coding. Threshold. Stimulus intensity/amplitude relationship of receptor potential and frequency of action potentials. Receptor threshold. Stevens' law. Receptors with exponent less than, equal to and greater than 1. Saturation. Adaptation: tonicity and phasicity. Modality of sensation. Appropriate stimulus. Receptor potential or generating potential.
-Somatic sensibility. Tactile sensitivity: tonic and phasic receptors, absolute threshold simultaneous spatial threshold. Lateral inhibition. Central pathways. Morphognosy, ilognosy, stereognosy. Vibration. Tickle.
Thermal sensitivity. Caloreceptors, frigoreceptors. Central pathways. Psychophysics of thermal sensation.
Pain sensitivity. Classification of receptors. Types of pain. Affirmatory system. Specificity of pain signal and mechanisms of stimulation. Wide dynamic spectrum neurons (allodynia) and specific neurons. Neurotransmitters and neuromodulators of pain. Sensitive tissues. Referred pain. Input and descending control of pain.
Proprioctivity. Mechanisms of receptor activation. Primary and secondary afferents of the neuromuscular spindle. Static and dynamic gamma innervation. Golgi muscle-tendon organ. Sensitivity to changes in length, velocity and force. Proprioceptive reflexes.
Skeletal and smooth muscle.
-Skeletal muscle. Ultrastructure of skeletal muscle. Organization into myofibrils and sarcomeres. Association of contractile and regulatory proteins. Contractile mechanism, interaction of cross bridges with thin filaments. Calcium and troponin.
-Electromechanical coupling. Function of T-tubules, receptors for dihydropyridine, ryanodine. Mechanisms of sarcoplasmic calcium recovery: ATP-dependent calcium pump, Ca2+/Na+ exchanger.
-Simple muscle shock. Shock summation and muscle tetanus. Role of ATP and energy supply.
-Biophysics of the contractile system. Muscle tension and loading. Isometric and isotonic contraction. Force, Length, Speed, Power. Tension-length relationship. Active, passive and total tension. Force-velocity relationship. Mechanical power.
-Motor units. Muscle fibers and motor units FF, FR, S, muscle fatigue, order of recruitment. Force control: recruitment and frequency (Renshaw's Inhibition).
-Smooth muscle. Unit and multi-unit smooth muscle. Function. Factors stimulating contraction. Smooth muscle action potential, hormonal, paracrine and stretch factors. Slow waves, myogenic tone. Pace-maker potentials. Electro-mechanical coupling. Transverse bridge cycle. Phasic and tonic contraction. Length-tension relationship, velocity force curve.