2024-25 Cell of the nervous system PDF version.pdf

Cellular structure of the nervous system Richard Wingate Learning objectives Students will understand: the structure properties of a typical neuron basic terms used to describe nervous system components how neurons conduct information and communicate with other neurons via different kind...

Cellular structure of the nervous system Richard Wingate Learning objectives Students will understand: the structure properties of a typical neuron basic terms used to describe nervous system components how neurons conduct information and communicate with other neurons via different kinds of synapses the basic classes of neurotransmitters the development, axes and subdivisions of the nervous system in relation to nerve cell types the significance of different types of neuron and glia to the functioning nervous system Neurons are densely packed Brainbow mouse – a transgenic animal where cells are given a random colour by combining three fluorescent proteins at different concentrations Where does one cell start and another end? Brainbow mouse Nerve cells have a complex architecture that was invisible to early scientists Purkinje’s brain globule The Golgi stain was widely adopted from the 1890’s The first hint that Purkinje cell the brain was a cellular structure Please remember that neurons are not balls and sticks Today’s lecture is in three parts Part 1: The structure of the neuron and how information is carried from dendrites to axons through to synapses Part 2: Different types of neurons and how their organisation gives rise to white and grey matter Part 3. Glia cell type and glial cell function and the origin of different types of neuron Part 1: Neurons Neurons are morphologically and functionally polarised The flow of electricity is different in dendrites and axons The synapse is the junction between neurons Neurotransmitters are released at synapses Neurotransmitter receptors are targets for drug design Synapses are a site of plasticity and learning Neurons are polarised Axon terminal (arborisation) Axon (single) Unidirection flow of information was one of the key propositiions of neuron theory of the cell body (soma) 1890’s Dendrites (multiple) Information is carried by graded potentials in dendrites Neuron cell membrane have unequal charge 0 distribution -70 mv Generated by pumping out Sodium (+ve) resting potential (-70 mV) outer is the difference between + - + - +- - + - Na + + + + + + ++ internal and external + ++ + + + charge 60% of the brain’s energy -- -- - - -- - -- - - - -- K + - + - + - +- consumed in providing inner ATP to fuel Na pumps Information is carried by graded potentials in dendrites Excitation of a dendrite causes 0 Local rebalancing of -70 mv membrane potential = depolarisation depolarisation spreads in outer all directions + - + - +- - + - ++ + ++ + - - - + + +++ signal decays over 1-2 mm - - - - - + - + +- - -- - - + - + - + - +- inner So where does polarisation of information flow arise? Information is carried by action potentials in axons axons have a different membrane structure 0 voltage-gated sodium -70 mv channel activated at a threshold (-50 mV) action potential action potential is self- outer regenerating and “all-or- + - + - +- - + - nothing” ++ + ++ + - - - + + +++ ++ ++ unidirectional ++ ++ -- -- - + + - + +- - -- - - + -+ + + + - + ++ - + - axon initial segment (hillock) inner Information is carried by action potentials in axons axons have a different membrane structure 0 voltage-gated sodium -70 mv channel activated at a threshold (-50 mV) 1mm/msec action potential is self- outer regenerating and “all-or- + - + - +- - + - nothing” ++ + ++ + - - - + + +++ ++ ++ unidirectional ++ ++ -- -- - + + - + +- - -- - - + -+ + + + - + ++ - + - graded potential travels inner 1mm in 20 msec Information is carried by action potentials in axons axons have a different membrane structure voltage-gated sodium channel activated at a threshold (-50 mV) action potential is self- outer regenerating and “all-or- + - + - +- - + - nothing” ++ + ++ + - - - + + +++ ++ ++ unidirectional ++ ++ -- -- - + + - + +- - -- - - + -+ + + + - + ++ - + - inner Synapses are the junctions at axon terminals electrical chemical electrical synapses couple cells gap junctions pores that allow current carried via ion transfer minimal delay bidirectional “couples” activity in neighbouring cells – synchronises a population gap junctions can be modulated Chemical synapses use neurotransmitters 0 presynaptic pre action potential neurotransmitters postsynaptic receptors 0.3-0.5 mSec unidirectional post receptor type determines whether postsynaptic cell is excited, inhibited or a Inhibition involves dropping the modulated long-term by resting membrane potential by pathway activation release of Chloride ions (hyperpolarization) Neurotransmitter receptors are potent drug targets biogenic amines acetylcholine, noradrenaline, adrenaline, dopamine and serotonin (5-HT) amino acids Glutamate, aspartate, g-aminobutyric acid (GABA), glycine peptides Somatostatin, endorphins, enkephalins, dynorphins, bradykinin, substance P other ATP, nitric oxide (NO) agonists and anatagonists of their receptors form the basis of many drugs Position of synapse on the post-synaptic neuron affects its influence on cell activity most distant – more electrically isolated D the closer the synapse to the axon initial segment, the more likely it is to trigger an A action potential Synpases can be classified by position axosomatic - cell body (very large potential effect on activity) axodendritic – dendrite (impact depends on proximity to axon) axoaxonic – single axon terminal (fine grain control over a single synapse)  light microscope Synaptic modification spines coat dendrites leads to learning dendrite synapses often found on dendritic spines synaptic protein axon dynamic spine morphology alters the amplitude of a synaptic dendritic spine signal electron microgaph Summary of Part 1 Neurons are morphologically and functionally polarised The flow of electricity is different in dendrites and axons The synapse is the junction between neurons Neurotransmitters are released at synapses Neurotransmitter receptors are targets for drug design Synapses are a site of plasticity and learning Part 2. Neurons to circuits Circuits are made of different kinds of neurons coronal section through temporal lobe cortex has six layers each with distinct kinds of neurons collectively shape the activity of Layer V projection neurons vi V iv iii ii i Cortical layers comprises of different neuron types projection neuron local interneurons (+ve, -ve) Motor, autonomic and sensory cells communicate to and from body motor neurons sensory neurons autonomic neurons Spinal cord: motor neurons are in ventral (anterior) “horn” motor control our muscles and are efferent )  Sensory cells project into dorsal (posterior) ”horn” from ganglia Afferent T-shaped sensory neurons receive signals about touch, pain, muscle stretch spinal ganglion spinal nerve cord Autonomic ganglia: receive input from pre- ganglionic neurons pre-ganglionic neurons parasympathetic control post-ganglionic cranial & sacral neurons and are efferent sympathetic thoracic central nervous (intermediate system horn) peripheral nervous system heart rate, respiration etc Communication over long distances enhanced by myelination insulating sheath with channel-rich gaps 7000 mm called nodes of Ranvier 1 mm rapid passive conduction over high resistance membrane segments Action potential regenerated myelin successively at sheath node channel-rich nodes saltatory conduction is 150 times faster Communication over long distances enhanced by myelination demyelinating diseases slow down or can even prevent conduction Grey and white matter spinal cord Grey and white matter brain white matter (stained black) – myelinated axons grey matter – cell bodies, dendrites, axons Summary of Part 2 different types of neurons make circuits inhibitory, excitatory types are determined by location of cell body, length and target of axon projection, interneuron, motor, primary sensory, pre- and post-ganglionic autonomic neuron long axons tend to be myelinated myelinated axons are grouped into “white” matter Part 3. Glia to the origin of neuronal diversity  microglia Glial cell types radial deposit myelin glia oligodendrocytes (CNS) oligodendrocyte (CNS) Schwann cells (PNS) phagocytic CNS microglia clear damaged tissue Schwann cell (PNS) physiological homeostasis blood vessel/brain interface astrocytes structure and development radial glia astrocyte Astrocytes astrocyte Brain homeostasis blood blood vessel/brain interface, vessel linking metabolism to function Sleep Signalling astrocyte recycling excess potassium at at at myelin gaps (nodes and synapses) recycling neurotransmitter synapse  Radial glia in Radial glia a transverse section of an adult spinal In the adult cord structural scaffold In development dividing radial “glial” cells give rise to neurons Radial glia in the embryo divide to give rise to neurons Birth of a neuron Red = nucleus Green = cytoplasm Yellow = neuron Paula Alexandre and Jon Clarke proliferation + migration radial and tangential Tangential migration dictate final migration position of neurons mantle migration defects often lead to cognitive impairment neurons embryonic spinal cord radial migration dividing glia ventricular zone Different neurons types are born at different locations embryonic spinal cord cells born at inner, dorsal ventricular surface dorsaling midline signal gradients of diffusible midline signals give different dorsoventral position types of neurons position determines neuron “type” ventralising signal ventral midline But what about neurons outside the neural tube in peripheral nervous system (PNS)? spinal sensory ganglion primary sensory neurons spinal post-ganglionic nerve autonomic neurons spinal cord PNS neurons migrate out of neural tube during neurulation as “neural crest” neurulation results in dorsal closure neural crest exits dorsal tube and neural populates PNS crest neural crest in embryonic mouse head dors al scanning electron Schematic of neurulation micrograph of neurulation with neural crest in blue stages Neurulation gives rise to a tube continuous inner lumen filled with cerebrospinal fluid rostrocaudal axis dorsoventral axis  Brain regions form along a rostrocaudal axis that flexes during development midbrain hindbrain spinal forebrain cord patterning on the midbrain dorsoventral axis telencephalon cell type diencephalon neuronal types are hindbrain modified according spinal to brain region cord Neural tube becomes the brain ventricles and spinal cord canal dorsal (superior) rostral dorsal (inferior) dorsal (posterior) ventral (anterior) caudal continuous cerebrospinal adult axes fluid filled cavities lateral ventricles in red  Neurulation defects range from spinabifida to a complete loss of head (anencephaly) anencephaly spinabifida classification craniorachischisis vertebral fusion meningocele meningomyelocele defect spinabifida cystica spina bifida five independent closures Summary of Part 3 Different types of glial cells have distinct morphologies relating to their different functions Astocytes regulate brain homeostasis Radial glia are neuronal progenitors Place of origin in the CNS determines neuron type PNS arises from neural crest neurulation characteristic associated birth defects