Lecture 1 and 2 - Intro to Neuroscience PDF

**[PM -- 275 -- Intro to neuroscience -- ]** THE NEURON -- Synapses occur mainly at the dendrite -- increase the surface area of the neuron. Positive and negative changes that occur on the synapse control whether the action potentials are sent. Axon hillock -- where first action potential is gen...

**[PM -- 275 -- Intro to neuroscience -- ]** THE NEURON -- Synapses occur mainly at the dendrite -- increase the surface area of the neuron. Positive and negative changes that occur on the synapse control whether the action potentials are sent. Axon hillock -- where first action potential is generated. Just before section of the myelin sheath. Unmyelinated action potential -- good for short distances don't require myelination e.g. mostly in brain. ESTABLISHING AND MAINTAINING A RESTING MEMBRANE POTENTIAL -- Action potential = rapid change in membrane potential transmitted along the axon then when reaches the synapse can release a chemical signal, difference in concentration of charged ions across the neuron. Neurons resting membrane potential determined by concentrations of ions, lipid bi -- layer and proteins that span membrane. K+ slightly higher inside, Na+ slightly higher outside membrane. Resting membrane potential maintained through removal of Na+ in exchange for K+ by Na+/K+ ATPase. ACTION POTENTIAL -- Rapid and reversible change in membrane potential where neurons transmit information. 'all or nothing' response. Concentration of charged ions change membrane potential. Frequency and pattern of firing of AP 'code' used by neurons to transmit info from source to target. GENERATING AN ACTION POTENTIAL -- Nonmyelinated axons -- conduction is slow (continuous) -- takes longer time for ions a channel protein gates to move. Myelinated axons -- conduction is fast (saltatory), myelin keeps in current axons, Aps generated in sheath gaps, quickly jump gap to gap. Process of myelination determines the positioning of the nodes of Ranvier. Myelination organises the axon to enable the transmission of action potential by saltatory conduction. All cell have membrane potential (difference in conc of ions across their membrane) -- neurons use changes in membrane potential as signals to receive, integrate and send info. Membrane potential changed by changing membrane permeability to ion -- produces graded potentials (local change sin membrane potential that degrade with distance) or action potentials (allow communication between neurons). Graded potentials can determine whether a neuron is excited and more likely to generate an action potential or inhibited and less likely to generate on at the axon initial segment. ACTION POTENTIAL DEPENDANT ON VOLTAGE -- GATED ION CHANNELS --  MYELINATING GLIA -- OLIGODENDROCYTES AND SCHWANN CELLS) Evolution of myelin sheath, ensures fast conduction by axons. Majority of axons myelinated in perinatal period, processes continue to adulthood. Myelination vital for coordination of movement. Continued proliferation, differentiation and myelin re-modelling in adults. GLIA -- Oligodendrocytes -- cell which generates all the myelin within the CNS. Metabolically active to generate lots of protein and lipids, nourishing layers that wrap around the axon. Restricted to CNS would not see in PNS. Schwann cells are restricted to PNS. Regenerating cells, constant turnover. MYELIN - Learning new skills is associated with changes in number and quality of contact between synapse, important for new learning and normal axon survival. Co-ordination drive by process of myelination. POTENTIAL TESTS FOR DEMYELINATION -- change in how fast an action potential is fired, able to detect the slowing electrical conduction e.g. diagnosis of MS -- visual evoked potential tests. LEUKODYSTROPHIES -- Disrupted growth of white matter in the brain. Inherited conditions which result in genetic change affecting quality of myelination. Primary lesion of myelin or oligodendrocyte. EXAMPLE -- Krabbe disease, improper processing of neurolipids, toxic to brain. Autosomal recessive condition resulting from deficiency in the enzyme GALC. GALACTOECEREBROSIDE -- responsible for liposomal hydrolysis of galactolipids formed during white matter myelination. Accumulation of galactosylsphingosine hugely toxic to oligodendrocytes and other cells. TYPES OF LEUKODYSTROPHIES - ASTROCYTE DIVERSITY AND INTERACTING PARTNERS -- ASTROCYTES -- modulate synaptic activity to clear neurotransmitters, provide metabolic support. Important for oligodendrocyte survival and promoting myelination. Important for communicating between neurons and the blood. Key component of blood brain barrier, couples neuronal activity with metabolic support from blood. Changes in function of astrocyte, change in normal synapse function e.g. loos/collapse of synapse. ASTROCYTES LEARNING AND MEMORY -- Improved synaptic function and ability to learn new tasks. Human astrocytes larger and more morphologically complex than rodent astrocytes, transplant astrocytes into the mouse brain and compared to controls. WHY IMPORTANT IN HUMANS -- fault in astrocytes e.g. alexander disease -- dominant gain of function in protein that's essential for the normal function of the astrocyte. Less capable of supporting astrocytes functions, so brain cant cope. ALEXANDER DISEASE -- disease of astrocytes -- cause by dominant gain of function mutations in glial fibrillary acidic protein (GFAP, expressed in astrocytes). Type of leukodystrophy characterised by abnormal protein deposits called Rosenthal fibres. Most cases begin before the age of 2. EPENDYMAL CELLS- Line all of the CSF filled space within brain and spinal chord. Provide physical barrier between CSF and brain. Constantly generating CSF -- rich in nutrients, helps clear waste products. Specialised ependymal cells form the CHOROID PLEXUS -- source of the CSF. Movement of cilia helps to circulate the CSF around ventricles and over brain. HYDROCEPHALUS -- (water on brain) -- cause by choroid plexus tumour or dysfunction in cilia motility (rare). MICROGLIA -- Defenders of the brain. Immune cells -- resident tissue macrophage only seen in CNS. Protects brain tissue from infection. Primary defence of CNS -- first response to injury or infection. General maintenance and surveillance -- remove cellular debris. Dysfunctional microglia -- disrupts normal brain homeostasis, neurotoxic causing neurodegeneration, common variants in microglial expressed genes, linked to increased risk of Alzheimer's. PET IMAGING of microglial density -- expression of TSPO (translocator protein) on mitochondrial membranes of microglia. Useful indicator of brain health, disease and response to treatment. SUMMARY --  NEUROANATOMY -- WHITE MATTER -- myelinated axons, thick, formation of tracts, commissural, association or projection of pathway. GREY MATTER -- axon terminals, dendrites, neuron cells bodies, less myelinated, signal processing/integration, initiates activity.  FRONTAL LOBE -- higher order function, how me make decisions about us. Degeneration of function -- people behave very weirdly. Sometimes in sports trauma constant damage to frontal lobe, lose executive decision making. PARIETAL LOBE -- central sulcus, one side motor cortex -- how we move and sensory cortex -- how we sense things, insula cortex. All defines frontal to parietal. 5 cortexes. CEREBELLUM -- helps with muscle tone, co-ordination and balance, also learning and memory processes. BRAINSTEM -- 3 parts -- midbrain, pons (bridging structure) and medulla oblongata (last part of brain stem attaching to spinal cord). Sensing body temp, HR, homeostasis and monitor oxygenation levels. Majority of cranial nerves exist here. 12 cranial nerves from brainstem -- brain stem sub divided into base and tegmentum. BASE -- contains motor tract. TEGMENTUM -- contains reticular formation and nuclei of cranial nerves. RETICULAR FORMATION -- contains vital centres -- resp, CV and coughing, sneezing. CEREBRAL HEMISPHERES -- WHITE MATTER -- communication between cerebrum and lower CNS structures. ASSOCIATION FIBRES -- connect different parts of same cortical hemisphere. COMMISSURAL FIBRES -- connect cortical hemispheres allow function as coordinated whole. Bundles of myelinated axons that link parts of the brain. PROJECTION FIBRES -- project to, or from, other CNS centres. E.g. motor neurons, axons project down through brainstem to spinal chord. SPINAL CHORD -- Continuation of brainstem. Individual nerves all connected. Transmit nerve impulses to and from the body. Enter at dorsal horn. Leave at ventral horn. 31 pairs of spinal nerves contact spinal chord via dorsal (sensory) and ventral (motor) roots. PERIPHERAL NERVOUS SYSTEM -- SENSORY RECEPTORS/FIBRES -- send info to the CNS along afferent pathway. Provide info on environment and sense cont. coming in MOTOR PATHWAY -- motor muscle activity in the body and arise in the CNS, efferent pathway. E.g. peristalsis. Exit. PERIPHERAL NERVES -- in sheaths surrounded by endoneurium. Protect from trauma and injury. Bundles of efferent and afferent axons. PERINEURIUM -- binds groups of axons into fascicles. EPINEURIUM -- encloses all fascicles to form nerve. CRANIAL NERVE -- VAGUS NERVE -- innervates neck, thorax and abdomen, axons performs somatic and autonomic function. PATHOPHYSIOLOGY -- disease and damage of peripheral nerves termed neuropathy. LEPROSY -- infection of peripheral nerves, chronic infection of skin, loss of sensation, muscle weakness and vision. A diagram of the nervous system Description automatically generated DEMYLEINATING DISEASES -- GUILLAIN -- BARRE SYNDROME (GBS) -- paralysing, life threatening disease of PNS. Caused by antibodies mistaking proteins of bacterium/ virus for those of node of Ranvier. Disrupted clusters of node of Ranvier = slow or blocked nerve conduction. SENSORY (AFFERENT) DIVISION -- Respond to stimuli (changes in environment at specific receptors). Classified dependant on what responding to e.g. mechanoreceptors, thermoreceptors, chemoreceptors, nocipcereceptors, photoreceptors. Mehcanoreceptors -- depolarised by stretch of the cell membrane. Location e.g. exteroceptors. Structure e,g. encapsulated and nonencapsulated. Sensory receptors can be free nerve endings (non -- encapsulated) or nerve endings are encapsulated by accessory cells, entire structure forms receptor.  MOTOR (efferent) DIVISIONS OF NS -- Initiated in CNS effect skeletal muscles (somatic), visceral muscles and glands (autonomic). How we respond to sensation. Motor ending are PNS elements activate effectors (muscles) by releasing NTs. Neuromuscular junction, motor ending of somatic motor nerves that innervate skeletal muscles. Peripheral nerves arise from brain stem (cranial nerves) and spinal chord (spinal nerves). Peripheral nerve fibres mostly 'mixed' and carry efferent and afferent projections. Sensory system receive signal from specialised sensory receptors for touch, temp, chemicals, light and pain into action potentials. Motor system effects skeletal muscles, viscera and glands.A diagram of a nerve cell Description automatically generated