Chapter 2- Objectives:

• I will be able to identify the journey of nerve cells

• I will be able to identify the critical periods.

• I will be able to identify and define plasticity

First Section/Introduction

• The connectivity of neurons is dependent on genetics and the environment

• Several diseases thought to only be in adults are now being considered in development

  • Likely due to improper pathway formation in early life

• Genes important in brain development may play a role in ASD

The Journey of Nerve Cells:

• Signaling molecules: molecules that “turn on” and “turn off” genes

• Signaling molecules begin the process of neural induction

  • Begins as embryo is developing

• The three main steps in the journey to becoming a neuron are induction, proliferation, and migration

  • Proliferation: the rapid reproduction of cells in an organism

  • Migration: the process by which newly formed neurons travel to their final destination

Induction:

• There are 3 embryonic layers:

  • endoderm: the innermost layer of cells in an embryo

  • ectoderm: the outermost layer of cells in an embryo

  • mesoderm: the middle layer of cells in an embryo

  • These layers eventually form into organs, bone, muscle, skin, and nerve tissue

    • This process of differentiation is controlled by mesoderm signaling molecules

• Neural Induction: the process by which some cells in the ectoderm differentiate into nervous tissue cells when they receive certain signaling molecules

  • Other molecules further differentiate these cells between neurons and glial cells

  • The portion of the ectoderm that doesn’t receive signaling molecules becomes the skin

• Sonic hedgehog: a specific signaling molecule secreted by mesodermal tissue lying beneath the future spinal cord

  • The proximity of cells to the sonic hedgehog secretion site determines what organ they will be

    • Adjacent nerve cells are converted to a class of glia

    • Cells farther away become motor neurons that control muscle

    • Cells exposed to an even lower concentration become interneurons

      • Interneurons: neurons that communicate w/ other neurons

  • This mechanism is similar in many other species

Migration

• Migration: the process by which neurons move to their proper positions in the brain

  • Begins 3 to 4 weeks after an embryo is fertilized

• The ectoderm starts to thicken and build up in the middle

  • The flat neural plate grows through cell division

  • Then the formation of parallel ridges starts

  • The ridges fold in on each other and fuse to form a hollow neural tube

• The top of the neural tube forms 3 bulges that will become the hindbrain, midbrain, forebrain

  • At week 7, the first signs of eyes and brain hemispheres appear

• Neurons move from the tube’s inner to outer surface

  • Division stops and the neurons form the intermediate zone (gradually accumulate as brain develops)

  • They then migrate to final destination with help of a variety of guidance mechanisms

• Glia aid in the guidance mechanism for neurons & provide scaffolding for ushering neurons to their destination

• Migration happens in an “inside-out” manner

  • Cells that arrive earliest make up the deepest layer of the cortex

• Inhibitory neurons: small neurons with short pathways usually found in CNS

  • Inhibitory neurons migrate in a straight line

• Overall, this is a very delicate process

• Alcohol, cocaine, and radiation prevent proper migration

  • This results in the misplacement of cells and may lead to mental retardation or epilepsy

  • Mutations in genes that regulate migration have been shown to cause some rare genetic forms of retardation and epilepsy in humans

Making Connections

• Neurons must make proper connections so their particular function can emerge

• The next phases of brain development are dependent upon environmental interactions

  • Birth and beyond: the reaction to listening to voices, toy responses, and even the temperature in the room can lead to more connections in neurons

• Interconnections happen through the growth of dendrites and axons

  • Axons enable connections between neurons at considerable distances

  • The axon can either be microscopic or very large

    • the axon of a motor neuron in the leg can travel from the spinal cord to the foot muscle

• Growth Cones: enlargements on an axon’s tip that actively explore environment as they seek out their precise destination

• Signaling molecules lie on cells that they contact or are released from sources found near the growth conecone

  • The binding of signaling molecules with receptors tells the growth cone whether to move forward, stop, recoil, or change direction.

  • These signaling molecules include:

    • Netrins

      • Vertebrate netrins guide axons around spinal cord

    • Semaphorins

    • Ephrins

      • Mostly families of similar molecules

    • Most of these proteins are common to many organisms

      • But these protein families are smaller in less evolved organisms

• Synapses: where axons make connections with other cells once they reach their target

  • At the synapse, the electric signal from the axon is transmitted by neurotransmitters to dendrites of other neuron

    • This can provoke or prevent the generation of new signal

  • Portion of axon contacting the dendrite becomes specialized for neurotransmitter release

  • Portion of dendrite contacting the axon becomes specialized for neurotransmitter reception

• These connections must be highly specific

  • Arises from mechanisms that guide axon to its target & molecules mediating target recognition when the axon meets the right neuron

    • Dendrites are actively involved in process of initiating contact with axons & recruiting proteins to the postsynaptic side of synapse

• Molecules pass between sending & receiving cells to make sure contact is formed properly & sending and receiving specializations are matched precisely

  • These processes ensure that the synapse can transmit signals quickly and effectively

• Other molecules coordinate maturation of synapse so it can accommodate changes as body matures and behavior changes

  • Defects in these molecules thought to make people susceptible to autism

  • Loss of these other molecules may underlie degradation of synapses that occurs during aging

• The combination of signals determines type of neurotransmitters that neuron will use to communicate with other cells

  • Some cells’ type is fixed, others aren’t

• When immature neurons are maintained in a dish with no other cell types they produce norepinephrine

  • If other cells are there they produce acetylcholine

• Signal to engage gene influenced by factors coming from location of synapse

Myelination

• Myelination: wrapping around axons by extensions of glial cells

  • Myelin increases speed by 100x

• Nodes of Ranvier: gaps between sections of myelin

• Saltatory conduction: the motion of the electrical signal when it jumps from one node to another

Paring Back

• The neural network is pared back to create a more efficient system

  • Around half of the neurons made in development survive to function in adults

• Apoptosis: programmed cell death

  • Neurons that need to be pared down are removed this way

  • Apoptosis occurs when the neuron loses a battle with other neurons to receive trophic factors

    • Trophic factors produced in limited quantities by target tissues

    • Each type of trophic factor supports the survival of a distinct group of neurons

      • E.g- Nerve growth factor is important for sensory neurons

  • Injuries and some neurodegenerative diseases kill neurons by activating cells death programs

• Brain cells form an excess amount of connections at first

  • Primates: projections from 2 eyes to brain overlap and then sort to their own territories for each eye

  • Young primate cerebral cortex: connections are greater in number & two times as dense

• Connections that are active survive while ones with little or no activity are lost

Critical Periods

• Most neuronal cell death occurs in the embryo

• The developing nervous system must get sensory, movement, or emotional input to mature properly in postnatal life

• Critical periods are characterized by high learning rates

• After the critical period, connections diminish in number and are less subject to change

  • Ones that remain are stronger, more reliable, and more precise

  • These turn into a variety of sensory, motor, or cognitive “maps” that reflect one’s perception of their worldworld

• The maturation of the frontal lobes is the last step in creation of adult brain

  • Function: judgment, insight, impulse control

  • Frontal lobe development continues into early 20’s

• Injury or deprivation of input occurring at specific stages of postnatal life can reshape the underlying circuit development

  • Loss of vision actually caused by loss of functional connections between eye and neurons in visual cortex

• Cognitive recovery from social deprivation, brain damage, and stroke is the greatest in early life

• Enriched environments support brain development

  • Children can learn languages/develop musical ability better than adults

• Higher activity in the critical period may contribute to higher incidences of disorders such as epilepsy

  • But as brain activity subsides many types of epilepsy fade away by adulthood

Plasticity

• Plasticity: the ability of brain to modify itself and adapt to challenges of environment

  • Plasticity is not unique to humans

• 2 types of plasticity:

  • Experience-expectant plasticity: developing functions to prepare for the experience to come

  • Experience-dependent plasticity: developing the function after the experience has happened