Pathological maturation of neurotransmitter systems in the developmental of Autism

Brain regions/ migration 1

Synaptic integration 1

Network activity/plasticity 1

Behavioral clinical phenotype

Glutamate

Cortical region

Blockade of GABAergic activities

Cortical excitatory inputs

Autism

Cortical region

(5HT2A) receptor activity on GABAergic interneurons

$Glutamate signaling

Developmental disorder such as Autism

Pyramidal and multipolar neurons

GABAergic neurons are sensitive to glutamate analog (NMDA)

Damage the large pyramidal and multipolar neurons

Autism

GABA

Cortex

Postnatal $ in cortical GABAergic neurons

Excitation and Noise in Cortex

Autism

Acetylcholine

Cerebral neocortex

$α4 β2 nicotinic acetylcholine receptor on GABAergic neurons

$GABAergic activity

Autism

Cerebellum

$α4, α2 nicotinic acetylcholine receptor

$GABAergic activity

Reported in autistic patients

Hippocampus

Prenatal stress

Level of acetylcholine

Developmental disorders including Autism

Cerebral cortex

$α4 β2 acetylcholine receptor

$Interneuron GABAergic neurotransmission

Autism

Serotonin

Cortex

Destruction of 5HT afferents by using Pchlorophenylalanine at a critical period(E12 to E17)

Abnormal distribution of GABAergic interneurons

Developmental disorders

Prefrontal cortex

5HT2A receptor agonists

Reduced GABAA currents by activation of protein kinase (PKC) which decreases GABAA mediated Cl currents

Autism

Prefrontal cortex pyramidal neurons

5HT4 receptor

±GABAA mediated current depending on Protein Kinase (PKA) levels

Autistic Spectrum Disorder

Dopamine

cerebral cortex

Pysiological changes in dopamine D1 and D2 receptors

Cause alteration in GABA neuron migration at the embryonic stage

Autism

Telencephalic regions

DAergic innervation

significant GABA dysfunction

Neuronal disorders including schizophrenia