3.3 - constructing neural circuits

multipolar neuron

neuron w/ one axon and more than one dendrite coming out of its cell body

• motor neuron

bipolar neuron

neuron w/ one axon and one dendrite coming out of its cell body

• retinal neuron

unipolar neuron

neuron w/ one extension coming out of its cell body

• extension splits into axon + dendrite extending opposite directions

• touch sensory neuron

anaxonic neuron

neuron w/ multiple dendrites coming out of its cell body, but no observable axon

• amacrine neuron

neurogenesis

formation of neuron from a neuronal precursor cell

gliogenesis

generation of glial cell from glial precursor cell

• AFTER neurogenesis

neurite

any extension growing out of neuronal cell body

neurogenesis steps

1. budding

2. outgrowth

3. axon specialization (axonogenesis)

4. dendrite formation (dendritogenesis)

5. maturation

when does a neuroblast become a neuron?

1. no cell division (post-mitotic)

2. elicit + respond to AP

3. can form synapses w/ each other or w/ non-neuronal targets

oligodendrocytes (CNS)

myelinate CNS neurons

astrocytes (CNS)

most abundant

• modulate synaptic transmission

• regulate ion concentrations around neurons

• provide nutrients to neurons

ependymal cells (CNS)

• form lining of ventricles

• facilitate nutrient supply

• filter out toxins

microglia (CNS)

• immune cells for CNS

• act as macrophages to clear cell debris + pathogens

Schwann cells (PNS)

myelinate PNS neurons

satellite cells (PNS)

astrocyte counterpart in PNS

• cover neuronal cell bodies

• regulated neuronal microenvironment

• provide nutrients to neurons

CNS neurogenesis phase

1. neuroepithelial cell - symmetrical division

2. radial glial cell - asymmetrical + symmetrical division

CNS gliogenesis phase

oliodendrocytes, astrocytes and ependymal cells are derived radial glial cells

PNS gliogenesis

neural crest gives rise to Schwann + satellite cells

neuronal migration

moves neuronal cell body to right location in NS

neurite pathfinding

neurons extend neurites to destined targets

both migration and pathfinding use__________

receptor-ligand interaction

• constructs precise neuronal network

why do neurites from different neuronal types have different migration paths?

1. receptor/ ligand binding specificity

2. axons w/ different neuronal types have different receptors

growth cone

structure at end of growing axon

• responsible for sensing environment + deciding whether/where an axon will grow

filopodium

forefront of growth cone

• rich in actin filaments + undergo constrant contraction + extension

• function: explore environment during pathfinding

lamellipodium

central region of growth cone behind filopodium

• rich in microtubules + vesicles

• function: membrane addition to enable axon elongation

what happens when the growth cone DOES NOT encounter appropriate guidance molecules?

1. filopodia extends to sense environment due to actin treadmilling

2. actin filaments slide backward + filopodia retreat due to:

• PM tension

• pulling back by microtubules

3. therefore NO net forward movement by growth cone

what happens when the growth cone DOES encounter appropriate guidance molecules?

1. filopodia extends to sense environment due to actin treadmilling

2. filopodial PM proteins interact w/ their ligands

3. this prevents actin filament + PMS from sliding backward

4. shrinkage of actin pulls the microtubules in the lamellipodium forward

• PM addition ensues → resulting in axon elongation

actin treadmilling

cytoskeleton monomers are removed from its - end and added to its + end

• moves cytoskeleton toward 1 direction

attractive neurite pathfinding

1. receptors on growth cone bind to attractive molecules

2. induces attractive signal transduction

3. modulates cytoskeleton

4. cone grows toward guidance molecules

repulsive neurite pathfinding

1. receptors on growth cone bind to repulsive molecules

2. induces repulsive signal transduction

3. modulates cytoskeleton

4. cone grows away from guidance molecules

attraction + repulsion before midline

1. axon grows toward midline due to attraction by netrin (attractive)

2. migrating axon does not have receptor for slit (repulsive), so it is not repelled

attraction + repulsion after midline

1. axon now loses receptors for netrin (attractive), so it is not attracted toward midline

2. axon now expresses receptors for slit (repulsive) instead

• thus repels away from midline

chemoaffinity hypothesis

proposes that neurons make connection based on their specific molecular interaction w/ their targets

3 major stages of synapse formation

1. formation/ initial contact

2. synaptic specialization

3. synaptic maturation

1. formation/ initial contact

trans-synaptic intraction btw proteins of 2 contacting neurons

• determines whether the 2 neurons are compatible to synapse

• once committed to form synapse, a synapse is established at the site of contact

2. synaptic specialization

proteins required to set up pre- and post- synaptic terminals are recruited to the site of contact btw 2 neurons in preparation to set up a synapse

3. synaptic maturation

recruited synaptic proteins have assembled into structures required for neurotransmission

• synapse is now ready for bi-direction communication btw the pre- and post-synaptic neurons

CNS formation/ initial contact

• early-stage contact

  • trans-synaptic interaction amoung adhesion molecules

• late-stage contact

  • mediated by presynaptic neurexin + postsynaptic neuroligin protein families

  • neurons now committed to form synapse

PNS formation/ initial contact

mediated by:

1. trans-synaptic interaction btw adhesion molecule NCAM on neuron + muscle fibril

2. binding of soluble Agrin + Wnt secreted by neuron to muscle MuSK receptor

3. retrograde influence of neuron by soluble factors NGF, FGF TGFb and Gdnf secreted by muscle fibril

CNS synaptic specialization

trans-synaptic protein interactions btw 2 contacting neurites:

1. decide whether 2 neurites will synapse w/ each other

2. determine the site of synapse formation (@ trans-synaptic interaction site)

3. recruit synaptic proteins to form synaptic terminals

PNS synaptic specialization

mediated by recruitment of synaptic proteins:

1. pre-synaptic = synaptic vesicle + active zone proteins

2. post-synaptic = synthesis + clustering of Ach receptors and associated signaling proteins

CNS synapse maturation - pre-synaptic specializations

• synaptic vesicle formation, and recycling pathways

• Nnurotransmitter synthesis + recycling pathways

• active zone w/ Ca²⁺ channel concentration and synaptic vesicle clustering w/in actin network

CNS synapse maturation - post-synaptic specializations

• formations of postsynaptic density

• actin cytoskeleton + scaffolding proteins localize neurotransmitter receptors to postsynaptic density

• neurotransmitter receptor signaling pathways

PNS synapse maturation - pre-synaptic criteria

can secrete Ach in response to APs and respond to retrograde signals from muscle

PNS synapse maturation - post-synaptic criteria

can respond to Ach by contracting + produce retrograde signaling molecules to modulate neurotransmission

rett syndrome

too few synapses

• possible cause = too little McCP2 protein?

  • protein regulates synapse numbers

• consequences = reduced synapses w/ decreased excitatory + inhibitory synaptic transmission

fragile-x syndrome

• possible cause = mutations in FMR1 gene (X-linked) leading to formation of excess dendritic spines capable of forming weak + unstable synapses

• consequences = excess but weak synapses

angelman syndrome

• possible cause = mutation in UBE3A gene resulting in loss of ubiquitin ligase

• consequences = excitatory neurons form properly but are unable to have LTP (long-term potentiation)

  • Resulting in excitatory/inhibitory activity imbalance in brain