NEURONS AND GLIA

Introduction “Neurophilosophy” Brain (neurons) is the origin of mental abilities Glia and Neurons Glia Insulates, supports, and nourishes neurons 90% of brain cells are glial cells Neurons Process information Sense environmental changes Communicate changes to other neurons Command body response

The Neuron Doctrine The birth of neurohistology Microscopy invention Discovery of fixation method for cutting thin slices Staining methods for selectively coloring parts of cells The Nissl Stain Developed by by the German neurologist Franz Nissl Stain the nuclei and surrounding material (Nissl body) Made it possible to distinguish neurons vs. glia and to study the arrangements of neurons in different parts of brain (cytoarchitecture) Fig2.1

The Neuron Doctrine The Golgi Stain Camillo Golgi discovered that by soaking brain tissue in a silver chromate solution, a small percentage of neurons became darkly colored in their entirety Soma (cell body or perikaryon) and neurites (axons and dendrites) Fig 2.3

The Neuron Doctrine Cajal’s Contribution Santiago Ramon y Cajal used Golgi stain method and worked out the circuitry of many regions of the brain : Father of neuroanatomy Golgi versus Cajal Reticular theory vs. cell theory Neuron doctrine Neurons communicate by contact, not continuity Final proof had to wait until EM got developed in the 1950s

The Prototypical Neuron The Soma ~20 um in diameter Cytosol: Potassium rich watery fluid inside the cell Organelles: Membrane- enclosed structures within the soma Cytoplasm: Contents within a cell membrane (e.g., organelles, excluding the nucleus) Fig2.7

The Prototypical Neuron The Axon Begins with axon hillock, initial tapered segment where action potentials are generated Rough ER does not extend into axon Protein composition of axon membarane is fundamentally different from that of soma No protein synthesis in the axon May extend from less than a millimeter to over a meter long May branch out (generally at right angles) to form axon collaterals that could return to the same cell (recurrent collaterals) Diameter ranges from less than 1  m to 25  m in humans - The speed of nerve impulses depends on axonal diameter

The Prototypical Neuron The Axon Terminal (terminal bouton) A site where the axon comes in contact with other neurons and passes information on to them Terminal arbor or boutons en passant Synapse - To fasten together Innervation - making synaptic contact Differences between the cytoplasm of axon terminal and that of axon No microtubules in the terminal Presence of synaptic vesicles (~50 nm in diameter) Dense covering of proteins on the inside surface of the synaptic membrane Large number of mitochondria (high energy demand)

The Prototypical Neuron Synapse Pre- and Postsynaptic sides : directionality of information flow Synaptic transmission Synaptic cleft Electrical-to-chemical-to- electrical transformation Neurotransmitter

The Prototypical Neuron Axoplasmic transport Wallerian degeneration Degeneration of axon when severed (axotomy) is due to the lack of protein synthesis machinery within axon Kandel Fig Anterograde transport by kinesin and retrograde transport by MAP-1C (dynein)

The Prototypical Neuron Slow Axoplasmic transport Paul Weiss’s experiment Tied off a sciatic nerve (axon) to find that material accumulate on the proximal side of the knot When the knot was untied, the bulged out accumulation continued down the axon The speed of movement was measured to be about mm per day ; SLOW AXOPLASMIC TRANSPORT Only anterograde direction Slow transport itself can be at two different speeds Slower ( mm per day) : fibrillar elements of cytoskeleton (neurofilament subunits, tubulins..) Faster (about twice as fast as the slower) : various cytosolic proteins (clathrin, actin, actin-binding proteins, enzymes..)

The Prototypical Neuron Fast Axoplasmic transport Bernice Grafstein Injected radioactive amino acids into somata Traced the synthesized (hot) proteins along the axon Large membraneous organelles are transported via fast transport Includes vesicles of the constitutive secretory pathways, synaptic vesicles precursor membranes, mitochondria, smooth ER elements.. ATP dependent but not protein synthesis dependent (once synthesized) Soma-independent (isolated axon still can transport

The Prototypical Neuron Dendrites Greek for ‘tree’ Dendritic tree for all the dendrites of a neuron “Antennae” of neurons - covered with thousands of synapses Dendritic membrane (postsynaptic membrane) contains many specialized receptors for neurotransmitters Dendritic spines Some neurons have these structures for receiving some types of inputs Discovered by Cajal Believed to isolate various chemical reactions Dynamic structures affected by the type and amount of inputs and developmental changes of environment Fig 2.17 Fig 2.18

Mental Retardation and dendritic spines Brain function depends on the highly precise synaptic connections, which are formed during the fetal period and are refined during infancy and early childhood 95% of population falls within two standard deviations from the mean of IQ (around 70 when the mean is set to be 100). Some 2-3% of humans with intelligence score below are considered to be mentally retarded IF the cognitive impairment affects the person’s ability to adapt their behavior to the setting in which they live Fig A Can have many causes Genetic disorders such as PKU or Down syndrome Accidents or infection during pregnancy or early childhood Poor nutrition during pregnancy Environmental impoverishment such as the lack of good nutrition, socialization, sensory stimulation during infancy Some with clear physical correlates (retarded growth, abnormal structures of head, hands, and body), most with only behavioral manifestations Dendritic spine abnormality has been found to be correlated with mental retardation

Classifying Neurons Classification Based on the Number of Neurites Unipolar cell Found in invertebrate nervous system - single process with different segments serving as receptive surfaces or releasing terminals Bipolar cell Two neurites Multipolar cell Most neurons in the brain are multipolar Kendal fig 2-4

Classifying Neurons Classification Based on Dendritic and Somatic Morphologies Often unique to a particular region of the brain Cortex - Stellate cells (star-shaped) and pyramidal cells (pyramid- shaped) Spiny or aspinous

Classifying Neurons Further Classification Based on connections within the CNS Primary sensory neurons motor neurons interneurons Based on axonal length Golgi Type I - projection neurons that extend their axons to other parts of the brain (e.g. pyramidal neurons in the cortex) Golgi Type II - local circuit neurons that have short axons that do not extend beyond the vicinity of cell body (e.g. stellate cells in the cortex) Based on neurotransmitter type Cholinergic, glutamatergic, GABAergic…

Glia ‘Sleeping Giants’ ? Function of Glia Supports neuronal functions Without glia brain cannot function! Astrocytes Most numerous glia in the brain Fill spaces between neurons Imporatant regulator of the chemical contents of extracellular spaces (Not much left after filling up) Envelop synaptic junctions - restrict the spreading of released neurotransmitters Possess their own neurotransmitter receptors!!

Glia Myelinating Glia Oligodendroglia (in CNS) and Schwann cells (in PNS) Insulate axons by wrapping axons around Myelin sheath One Oligodedroglia can provide insulation to several axons but each Schwann cell does to a only a single axon Node of Ranvier Region where the axonal membrane is exposed

Glia Other Non-Neuronal Cells Microglia as phagocytes (immune) Ependymal cells provide lining of fluid- filled ventricles and directs cell migration during brain development Vasculature