Development of neurotransmitters Flashcards
What 3 things does the nervous system vary in?
1) Types of cells
2) Chemical properties
3) Electrical properties
Why is variation in the nervous system important?
- Important to build complex circuits which can be optimised to do particular jobs
How is the spinal cord different to the neural tube?
- Looks different
- Multiple layers, which have migrated away from the developing neural tube
Where do afferents from the DRG target in the spinal cord?
Different layers, depending upon what the input it (eg. pain, touch, proprioception)
What specifies where neurons will be born in the layers of the spinal cord?
A 2-dimensional grid made from the A-P and the D-V axis
What do TFs specify?
Neural cell types which emerge at particular positions and developmental stages - by regulating transcription of other genes in these cells
What defines a specific neuronal subtype?
TF combinations expressed by the cell
What is the evidence that BMPs and Wnts are involved in D-V patterning?
Loss of GDF7 leads to the loss of D1A neurons, but NOT D1B neurons
What happens if Wnt signalling is enhanced?
Dorsal gene expression domain expanded ventrally
What happens if Wnt signalling is reduced?
Ventral gene expression domain is expanded dorsally
What does changing Wnt expression interfere with?
Patterning/fate but NOT differentiation (neurons are still produced - BMP antagonists)
What happens to neural identity over time?
It changes
What helps to set up interneuron domain BOUNDARIES?
CROSS-REPRESSION between transcription factors:
- TF promote gene expression in their target and repress TF which would have defined a neighbouring region
- Forms ‘striped domains’
What does TF cross-antagonism refine?
The pattern laid down by BMP/Wnt/Shh signalling
How are neuronal subtypes different to each other?
- Express different neurotransmitters
- Different migratory pathways
- Different receptors
- Different axonal projections
- Different circuit integration
Which dorsal neurons end up in the ventral horn?
dl1 neurons
How is migration of neurons different in the cortex to in the spinal cord?
In the cortex - linear migrations
In the spinal cord - many migratory pathways cross over
How do migratory maps of neurons differe?
Differ at different rostro-caudal positions
What happens to neurons post mitotically?
- Specification
- Maturation
- NT expression
- NT receptor expression
- Dendrite axon extension
- Circuit assembly
What encodes the FEATURES of an axon? (NT, dendrites, receptors etc)
TF expressed in the cell when it reaches a post mitotic state
What encodes the FUNCTION/INNERVATION of an axon?
Where they are born
What is the difference between DiLa and DiLb neurons in the spinal cord and in the hindbrain? (at the same position in the dorsal horn)
In the spinal cord - form 2nd order neurons
In the hindbrain - innervate the trigeminal nucleus
What determines if the neuron is inhibitory or excitatory?
Expression of different transcription factors (different genes switched on)
Out of DiLA and DiLB neurons, which are excitatory?
DiLB
Out of DiLA and DiLB neurons, which are inhibitory?
DiLA
What determines what neurotransmitter is expressed in an inhibitory/excitatory neuron?
Different transcription factors expressed in each neuron
How are circuits made with neurons?
TF expression drives migration and maturation
TF in specific patterns induce different neurotransmitter phenotypes in different neurons
AS A RESULT:
- Get SPECIFIC neurons in SPECIFIC places with SPECIFIC features
- Can connect to the targets that they need to (they are in the right place, with the right receptors, with the right NT)
(pre-programmed)
Where are motor neurons in the spinal cord?
In the ventral horn