Module 3: Construction of Neural Circuits

how are cells in different regions linked?

axon pathways and synaptic connections

what is a neurite?

an immature axon and dendrite

what do neurites develop into?

one becomes an axon, the other becomes a dendrite

what is a growth cone?

specialized structure found at the end of a growing axon

what is a growth cone made out of?

lamellipodium and filopodia

what is the lamellipodium?

sheetlike structure found at the tip of an axon

what is the filopodia?

fingers extending from the lamellipodium, can form and disappear

why is the motility of the growth cone important?

it helps to adjust to a rapidly changing environment via monomerization and polymerization, made of actin, tubulun, dynein, and myosin

how are growth cones steered?

they detect guidance cues in extracellular matrix or by contacting other cells, growth cones have receptors on their outer surface, these cues can activate signaling pathways which regulate how the cytoskeletal molecules will behave

what are the different classes of axon guidance cues?

extracellular matrix molecules (ECM), cell adhesion molecules (CAMs), netrins, slit, and semaphorins

what is the extracellular matrix molecule?

contain large molecules that are embedded within them such as (laminins, collagens, and fibronectin), bind to integrins on the growth cone and form adhesion complexes which helps to create a durable surface for which the axon can grow on

what are cell adhesion molecules?

help cells stick to each other

homophillic bonding

one type of cell adhesion molecule will recognize another same type of cell adhesion molecule and bind to it

what is homophillic binding important for?

fasciculation

what is fasciculation?

the bundling of axons as they grow

where are netrins found?

found on the surfaces of cells at the midline of the nervous system

how do netrins function?

bind to DCC receptors on growth cones

what are netrins important for?

the development of axon pathways that must connect two sides of the nervous system

what is an example of a cell adhesion molecule?

L1, cadherins, and NCAM

what is an example of a netrin molecule?

formation of commisure fissures

what is the signaling pathway for netrin?

DCC receptors, Rho/GAP activates molecular switches, changes to actin, axons attracted across the midline

where are SLIT cells found?

midline of cells of the nervous system growth cone

when are robo receptors activated for SLIT cells?

after axons cross the midilne

what does SLIT do?

causes growth cone to no longer be resonsive to netrin and prevents re-crossing of axons

what receptors activate SLIT cells?

robo

what is a semaphorin?

a chemorepellant that tells growth cones to go away

what is the signaling pathway for semaphorin?

bind to plexin and neuropilin receptors on growth cones, activates GTPase RhoA, leading to growth cone collapse or retraction

what is a topographic map?

the body’s surface and features of external world are mapped onto the brain

what is a retinotopic map?

adjacent points in visual space are represented by nearby neurons in the brain

what is the chemoaffinity hypothesis?

growing neurons reach their target cells by recognizing molecular tags

Roger Sperry’s Frog Experiment and the Chemoaffinity Hypothesis (what was it)

crushed the optic nerves of the frogs and let them regenerate (they grew back to their original locations) rotated the eyes 180 degrees, crushed the optic nerves, and let them regenerate (optic nerves grew accorrding to anterior-posterior mapping and led to behavioral confusion in the frogs) found that optic nerve axons project from the retina of the eye to precise locations in the optic tectum by recognizing signals from the tectum, regardless of eye orientation

what are the molecular tags for the visual system?

optic tectum = ephrin ligand, growth cones = Eph receptors

how do the molecular tags of the visual system function?

Eph receptors on growth cones grow to low levels of ephrin ligands on the optic tectum and vice versa

what is synaptogenesis?

development of communication between neurons, develops 12 to 9 months post natal

how is a presynaptic terminal made?

growth cone slows down and makes physical contact with target cells

what is the molecular mechanism for the creation of a synapse?

growth cone makes physical contact with target cell, cadherins and protocadherins recognize the contact between the two neurons.

what are the molecular cues for creating a synapse

synaptic cell adhesion molecules (syn AM), neurexins (presynaptic) and neuroligins (post-synaptic)

what is the anatomy of the synapse?

presynaptic terminal and postsynaptic density

what is a trophic interaction?

long-term dependency of a neuron on their 1synaptic targets

what is a neurotrophin?

regulate differentiation, survival, and growth of neurons

what is a nerve growth factor (NGF)?

a type of neurotrophin, can cause neurons to grow very largely

not all neuron types have the same effect with a neurotrophin, why?

different neurons have different receptors expressed for neurotrophins, tyrosine kinase (TrK) bond mature forms of neurotrophins for survival, p75 receptors bind to immature neurotrophins for cell deat

what is neurogenesis?

the creation of neurons

what is BDNF

brain-derived neurotrophic factor that helps neurogenesis occur in adult brains