http://www.back-in-business-physiotherapy.com/images/files/DescendingControl.pdf

Descending control of pain.

Autism is a severe neurobehavioral syndrome, arising largely as an inherited disorder, which can arise from several diseases. Despite recent advances in identifying some genes that can cause autism, its underlying neurological mechanisms are uncertain. Autism is best conceptualized by considering the neural systems that may be defective in autistic individuals. Recent advances in understanding neural systems that process sensory information, various types of memories and social and emotional behaviors are reviewed and compared with known abnormalities in autism. Then, specific genetic abnormalities that are linked with autism are examined. Synthesis of this information leads to a model that postulates that some forms of autism are caused by an increased ratio of excitation/inhibition in sensory, mnemonic, social and emotional systems. The model further postulates that the increased ratio of excitation/inhibition can be caused by combinatorial effects of genetic and environmental variables that impinge upon a given neural system. Furthermore, the model suggests potential therapeutic interventions.

https://onlinelibrary.wiley.com/doi/epdf/10.1034/j.1601-183X.2003.00037.x

Model of autism: increased ratio of excitation/inhibition in key neural systems

How Inhibition Shapes Cortical Activity

Developing networks follow common rules to shift from silent cells to coactive networks that operate via thousands of synapses. This review deals with some of these rules and in particular those concerning the crucial role of the neurotransmitter gamma-aminobuytric acid (GABA), which operates primarily via chloride-permeable GABA(A) receptor channels. In all developing animal species and brain structures investigated, neurons have a higher intracellular chloride concentration at an early stage leading to an efflux of chloride and excitatory actions of GABA in immature neurons. This triggers sodium spikes, activates voltage-gated calcium channels, and acts in synergy with NMDA channels by removing the voltage-dependent magnesium block. GABA signaling is also established before glutamatergic transmission, suggesting that GABA is the principal excitatory transmitter during early development. In fact, even before synapse formation, GABA signaling can modulate the cell cycle and migration. The consequence of these rules is that developing networks generate primitive patterns of network activity, notably the giant depolarizing potentials (GDPs), largely through the excitatory actions of GABA and its synergistic interactions with glutamate signaling. These early types of network activity are likely required for neurons to fire together and thus to "wire together" so that functional units within cortical networks are formed. In addition, depolarizing GABA has a strong impact on synaptic plasticity and pathological insults, notably seizures of the immature brain. In conclusion, it is suggested that an evolutionary preserved role for excitatory GABA in immature cells provides an important mechanism in the formation of synapses and activity in neuronal networks.

GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations

In the mature brain, GABA (gamma-aminobutyric acid) functions primarily as an inhibitory neurotransmitter. But it can also act as a trophic factor during nervous system development to influence events such as proliferation, migration, differentiation, synapse maturation and cell death. GABA mediates these processes by the activation of traditional ionotropic and metabotropic receptors, and probably by both synaptic and non-synaptic mechanisms. However, the functional properties of GABA receptor signalling in the immature brain are significantly different from, and in some ways opposite to, those found in the adult brain. The unique features of the early-appearing GABA signalling systems might help to explain how GABA acts as a developmental signal.

Is there more to gaba than synaptic inhibition

https://www.neuronetwork.unibas.ch/events/documents/Schuler_2001.pdf

Norman Klix

Papers

Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABA(B) responses in mice lacking GABA(B(1))