neurodevelopment & neuronal plasticity

what are the stages of brain development?

• cell birth/proliferation (neurogenesis and gliogenesis)

• cell migration

• cell differentiation and maturation

• synaptogenesis and synaptic pruning

• cell death

• myelination (myelogenesis)

describe neurogenesis

• at its peak, 250,000 neurons are born per minute

• does not take place with neuronal division - neurons do not divide

• as the neural tube widens, the extensions of the cells elongate still holding on to the outer wall

describe cell birth/proliferation

• stem cells divide to form progenitor (precursor) cells

• each progenitor cell can be a neuroblast or glioblast

• cells undergoing mitosis are always closer to the inner surface of the neural tube (ventricular zone)

describe cell migration

• refers to the movement of newly formed cells towards the outer layers

• occurs with the help of chemical signals and physical support (provided by radial glia)

how does the cortex develop?

• develops in an inside-out manner

• there is a primitive map of it that predisposes cells born in a certain region to migrate to a certain cortical location

what do radial glia do?

provide support to the newly formed cells/neurons?? to help them migrate to where there supposed to be

migration of young neurons after birth

• a large wave of neurons are still migrating in the frontal cortex after birth

• most prominent in the first few months of life (typically up to 3 but can continue until 7 months)

• most of these will become inhibitory GABAergic interneurons

describe differentiation and maturation

• after arriving at their destinations, immature neurons begin to express particular genes that will allow them to specialise

• they start to form an axon (mm/day) and dendrites (μm/day) that will give them their distinctive shape

what are the processes in dendritic development?

• dendritic arborization (branching)

• growth of dendritic spines

what do dendritic spines do?

provide more space for the neurons??

what is induction?

cells influence the fate of their neighbouring cells through ongoing cell-cell interactions via the secretion of chemicals

what is pluripotency?

• the process of replacing immature cells that were removed from a region with new neurons that with acquire the same characteristics

• once cells mature and differentiate, they lose this ability

what is a growth cone?

• the growing end of the axon (has extreme chemical sensitivity)

• they develop thin extensions called filopodia

• they are attracted to chemicals released from target sites (cell adhesion molecules; tropic molecules)

describe synaptogenesis

• after successful contact, the axon and target induce each other to construct machinery to help them attach and form a synapse

• synapses are initially slow in their firing compared to more mature brains

• majority of synapses forms after birth

how do filopodia move?

• advance by adhering to other cells (contact guidance) or can be chemically guided (chemotropism) - can be attractive or repulsive

• proteins on their membrane serve as receptors that ‘recognise’ various molecules that they will (not) adhere to

describe synaptic pruning

• successful and active synapses are maintained

• non-successful synapses are eliminated (pruned)

• evidence of plasticity in the brain

• occurs more during adolescence

describe the study by Gogtay et al (2004)

• did brain scans of 4-25y olds every 2 years and found that grey matter thickens in childhood but then it begins to thin out gradually

• Synaptic pruning starting from the back to the front by early adulthood

• Increase in white matter (myelination) which peaks in adulthood

• Perhaps a second phase of “use it or lose it”

• The process is completed earlier in girls than in boys

describe cell death

• apoptosis - programmed cell death (PCD); an active process

• occurs in plants and animals

• elimination of the overabundance of cells (and their synaptic connections)

what is necrosis?

• the death of body tissue; passive process

what determines which cells live and die?

• proteins secreted by target cells promote the survival and growth of neurons (survival glands)

• nerve growth factor (NGF)

• there are several proteins - a family of these factors called neurotropic factors

• to avoid apoptosis a neuron needs neurotrophins (growth factors) from its target cells and active communication with other neurons strengthening the synapses

describe myelination

• refers to the process by which glia form the fatty sheath that covers the axon of neurons

• myelin speeds up the transmission of the neural impulses

• first occurs in the spinal cord → hindbrain → midbrain → forebrain

• slow process - occurs over decades

how does myelination affect motor behaviour?

• correlation between myelination and ability to grasp

does the brain produce new neurons in adulthood?

• yes, there are a few neurogenic regions in the adult human brain

• olfactory epithelium contains cells that continuously divide to provide new olfactory sensory neurons and replace damaged ones

• cells in the subventricular zone of the lateral ventricle migrate to replace interneurons in the adult olfactory bulb (rostral migratory stream)

new neurons in the hippocampus

• granular layer of the dentate gyrus was the first neurogenic area to be discovered

• new neurons are created and added to the dentate gyrus throughout life

new neurons in the cerebral cortex

• very few adult-born neurons in the cortex

• neurogenesis can be induced by injury but it depends on the extent of the injury

• recovery is better in younger brains than older brains and better in the periphery than in the brain

• involves collateral sprouting - new branches formed by non-damaged axons attach to vacant spots of dendrites; the cells secrete neurotophins that allow collateral sprouting to occur

describe the study by Burton et al. (2002)

• asked blind and sighted people to feel braille letters or other items and say whether they were the same or different

• blind people performed better

• brain scans showed substantial activity in the occipital cortex of blind people

• auditory stimuli also produced increased responses in visual areas of the cortex

how does experience affect brain development?

• rats raised in an enriched environment develop a thicker cortex and have increased dendritic branching

• mostly due to physical activity

• increased dendritic branching was correlated with improved ability to learn

what is a critical period?

a time frame where the brain is most sensitive to a specific experience