Photographs of Human Fetal Brain Development Lateral view of the human brain shown at one-third size at several stages of fetal development. Note the gradual emergence of gyri and sulci.

Phases of brain development Neural plate induction Neural proliferation Migration & Aggregation Axon growth & Synapse formation Cell death & Synapse rearrangement

Induction of the Neural Plate 2-3 weeks after conception A patch of tissue on the dorsal surface of the embryo that will become the nervous system Development induced by chemical signals “growth factors”: several chemicals produced in developing and mature brain that stimulate neuron development and help neurons respond to injury

cephalic flexure cervical flexure

~19 days ~23 days

Phases of brain development Neural plate induction Neural proliferation Migration & Aggregation Axon growth & Synapse formation Cell death & Synapse rearrangement

2. Mitosis/Proliferation Generation of new cells 3 swellings at the anterior end in humans will become the forebrain, midbrain, and hindbrain Occurs in ventricular zone Rate can be 250,000/min After mitosis “daughter” cells become “fixed” post mitotic

Phases of brain development Neural plate induction Neural proliferation Migration & Aggregation Axon growth & Synapse formation Cell death & Synapse rearrangement

3. Migration: slow movement to the “right place” Only a soma and immature axon at this point -undifferentiated at start of migration. But, differentiation begins as neurons migrate. They develop neurotransmitter making ability, action potential

3. Migration Radial Glia Radial glial cells act as guide wires for the migration of neurons Migrating cells are immature, lacking dendrites Cells that are done migrating align themselves with others cells and form structures (Aggregation)

Growth Cones: tips of axons on migrating, immature neurons Growth cones crawl forward as they elaborate the axons training behind them. Their extension is controlled by chemical cues in their outside environment that ultimately direct them toward their appropriate targets.

5 Phases of Neurodevelopment Neural plate induction Neural proliferation Migration & Aggregation Axon growth & Synapse formation Cell death & Synapse rearrangement

4. Axon Growth/Synaptogenesis Once migration is complete and structures have formed (aggregation), axons and dendrites begin to grow to their “mature” size/shape. Axons (with growth cones on end) and dendrites form a synapse with other neurons or tissue (e.g. muscle) Growth cones and chemo-attractants are critical for this.

Synaptogenesis Formation of new synapses Depends on the presence of glial cells – especially astrocytes Chemical signal exchange between pre- and postsynaptic neurons is needed

5 Phases of Neurodevelopment Neural plate induction Neural proliferation Migration & Aggregation Axon growth & Synapse formation Cell death & Synapse rearrangement

5. Neuronal Death Between 40-75% neurons made, will die after migration – death is normal and necessary !! Neurons die due to failure to compete for chemicals provided by targets Neurotrophins – promote growth and survival guide axons stimulate synaptogenesis

Synaptic rearrangment Release and uptake of neurotrophic factors Neurons receiving insufficient neurotropic factor die Axonal processes compete for limited neurotrophic factor

Synaptic rearrangment, cont’d: Myelination Time after synaptogenesis

Postnatal Cerebral Development Human Infants Postnatal growth is a consequence of Synaptogenesis Increased dendritic branches Myelination (prefrontal cortex continues into adolescence) Overproduction of synapses may underlie the greater “plasticity” of the young brain Young brain more able to recover function after injury, as compared to older brain

Neural Tube Defects (NTDs) 1- Spina Bifida Oculta Meningocele Meningomyelocle cystica Rachischhisis

meningocele occulta meningomyelocele myeloschesis

10 %of normal people L5 or S1

Neural Tube Defects (NTDs) 1- Cranial Bifida Cranial Meningocele Meningoencephalocele Meningohydroencephalocele Anencephaly

Cranial Bifida Meningoencephalocele Cranial Meningocele Meningohydroencephalocele Cranial Meningocele

Histology of the Nervous System

The Nervous system has three major functions: Sensory – monitors internal & external environment through presence of receptors Integration – interpretation of sensory information (information processing); complex (higher order) functions Motor – response to information processed through stimulation of effectors muscle contraction glandular secretion

General Organization of the nervous system Two Anatomical Divisions Central nervous system (CNS) Brain Spinal cord Peripheral nervous system (PNS) All the neural tissue outside CNS Afferent division (sensory input) Efferent division (motor output) Somatic nervous system Autonomic nervous system

Histology of neural tissue Two types of neural cells in the nervous system: Neurons - For processing, transfer, and storage of information Neuroglia – For support, regulation & protection of neurons

Neuroglia (glial cells) CNS neuroglia: astrocytes oligodendrocytes microglia ependymal cells PNS neuroglia: Schwann cells (neurolemmocytes) satellite cells

Astrocytes create supportive framework for neurons create “blood-brain barrier” monitor & regulate interstitial fluid surrounding neurons secrete chemicals for embryological neuron formation stimulate the formation of scar tissue secondary to CNS injury

Oligodendrocytes create myelin sheath around axons of neurons in the CNS. Myelinated axons transmit impulses faster than unmyelinated axons Microglia “brain macrophages” phagocytize cellular wastes & pathogens

Ependymal cells line ventricles of brain & central canal of spinal cord produce, monitor & help circulate CSF (cerebrospinal fluid)

Peripheral neuroglia 1- schwann cell 2- satellite cell

Schwann cells surround all axons of neurons in the PNS creating a neurilemma around them. Neurilemma allows for potential regeneration of damaged axons creates myelin sheath around most axons of PNS Satellite cells support groups of cell bodies of neurons within ganglia of the PNS

Neuron structure

Most axons of the nervous system are surrounded by a myelin sheath (myelinated axons) The presence of myelin speeds up the transmission of action potentials along the axon Myelin will get laid down in segments (internodes) along the axon, leaving unmyelinated gaps known as “nodes of Ranvier” Regions of the nervous system containing groupings of myelinated axons make up the “white matter” “gray matter” is mainly comprised of groups of neuron cell bodies, dendrites & synapses (connections between neurons) of Ranvier

Classification of neurons Structural classification based on number of processes coming off of the cell body:

Anaxonic neurons no anatomical clues to determine axons from dendrites functions unknown

Multipolar neuron multiple dendrites & single axon most common type

Bipolar neuron two processes coming off cell body – one dendrite & one axon only found in eye, ear & nose

Unipolar (pseudounipolar) neuron single process coming off cell body, giving rise to dendrites (at one end) & axon (making up rest of process)

Classification of neurons Functional classification based on type of information & direction of information transmission: Sensory (afferent) neurons – transmit sensory information from receptors of PNS towards the CNS most sensory neurons are unipolar, a few are bipolar Motor (efferent) neurons – transmit motor information from the CNS to effectors (muscles/glands/adipose tissue) in the periphery of the body all are multipolar Association (interneurons) – transmit information between neurons within the CNS; analyze inputs, coordinate outputs are the most common type of neuron (20 billion) are all multipolar

Conduction across synapses In order for neural control to occur, “information” must not only be conducted along nerve cells, but must also be transferred from one nerve cell to another across a synapse Most synapses within the nervous system are chemical synapses, & involve the release of a neurotransmitter

The Structure of a Typical Synapse

Anatomical organization of neurons Neurons of the nervous system tend to group together into organized bundles The axons of neurons are bundled together to form nerves in the PNS & tracts/pathways in the CNS. Most axons are myelinated so these structures will be part of “white matter” The cell bodies of neurons are clustered together into ganglia in the PNS & nuclei/centers in the CNS. These are unmyelinated structures and will be part of “gray matter”

Neural Tissue Organization

Anatomical structure of Nerves Fig. 14.6