Synaptic dysfunction in neurodevelopmental disorders

Question 1

What is the name of the structure that allows ion flow between neurons at electrical synapses?

Answer 1

Gap junctions

Question 2

What is the main advantage of electrical synapses?

Answer 2

Faster signal transmission, ideal for synchronous behaviours

Question 3

When does synapse initiation, maturation and pruning occur during the development of the rodent cortex?

Answer 3

P0-P21

Question 4

When do synapses show mature morphology in the rodent cortex?

Answer 4

P21-P30

Question 5

At which developmental stages do synaptogenesis, myelination, and synaptic pruning occur in humans?

Answer 5

Synaptogenesis: prenatal to early childhood
Myelination: prenatal to early adolescence
Synaptic pruning: early childhood to adolescence

Question 6

Manifestation of neurodevelopmental disorders correlate with which stages of the synaptic development in humans?

Answer 6

Synaptogenesis
Myelination
Synaptic pruning

Question 7

True or false: NDDs tend to co-occur.

Answer 7

True: e.g., individuals with autism spectrum disorder often have intellectual disability, and many children with attention-deficit/hyperactivity disorder (ADHD) also have a specific learning disorder.

Question 8

What are the two main families of etiological factors explaining NDD?

Answer 8

External: environment (global), agents (specific)
Internal: biology and genetics

Question 9

What sort of protein family is shank belonging to?

Answer 9

Postsynaptic density proteins

Question 10

What is shank3?

Answer 10

A postsynaptic density protein invovled in the structural organization of dendritic spines

Question 11

On which gene is located Shank3? Why does its location make it prone to haploinsufficiency? What disorder is related to the loss of one functional copy of Shank3?

Answer 11

At the end of chromosome 22 -> if chromosome is degraded on that end, one copy of the gene is lost

Phelan-McDermid Syndrome

Question 12

What is a central question concerning the many isoforms of Shank3?

Answer 12

It is yet to determine whether different Shank3 isoforms are expressed in different functional and morphological neuron types.

Question 13

How can Shank3 be involved both in autism and schizophrenia?

Answer 13

Via different mutations.

Question 14

If deficiency in Shank3 could be rescued in the adult brain, could any function be recovered? How does recovery relate to developmental stages?

Answer 14

Yes, as shown with Cre/Lox experiments (tamoxifen).

Recovery can only be maximized when carried out during critical periods (plasticity)