Chapter 2: The Developing Brain

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