Bebeklerde P50 Duyu Yolluk

P50 sensory gating is thought to reflect a complex interaction of inhibitory neurocircuits located primarily in the hippocampus, dorsolateral prefrontal cortex, and thalamus¹⁶. Thus, alterations in P50 sensory gating in infants may suggest altered development in these regions of the brain.

In these brain regions, GABAergic interneuron inhibition of glutaminergic pyramidal cells likely accounts for the gating process, with the inhibition provided by GABAergic cells. The GABAergic interneurons are themselves modulated by adrenergic and cholinergic input. The adrenergic input is intermittent and inhibits the interneurons which decreases their ability to inhibit pyramidal cells and thus blocks sensory gating. One of the difficulties in recording awake infants is that even very mild stressors, such as applying electrodes, can increase adrenergic tone an interfere with the ability to measure functional gating abilities.

In contrast to the impact of intermittent adrenergic input, cholinergic stimulation of interneurons is tonic and results in enhanced interneuron firing, thus improving sensory gating¹⁷. Factors which decrease cholinergic input, such as genetic phenotypes related to decreased cholinergic receptor expression, lead to chronic problems in sensory gating¹⁸. Similarly, decreased neuronal release of choline, as occurs during non-REM sleep, also decreases interneuron activity and sensory gating. Nicotine is an interesting compound as acute use stimulates nicotinic cholinergic receptors and improves sensory gating^19,20, while repeated or chronic nicotine use has no effect when used alone but blocks the effects of other agonists²¹, presumably because chronic stimulation leads to receptor desensitization²². Infants who are exposed to prenatally exposed to nicotine through maternal cigarette use have impaired P50 sensory gating¹².

This awareness of the fundamental biology of sensory gating was the rationale for a randomized trial of supplementation during pregnancy with the dietary component choline, an agonist at the cholinergic receptor on interneurons. Supplementation occurred in from early in the second trimester through approximately 3 months post birth. Infants who had received choline supplementation had accelerated development of sensory gating¹⁵.

Infant P50 sensory gating ratio assessment is feasible²³, reliable²⁴, and stable between infancy and four years of age²⁵. Impairments in infant P50 sensory gating are associated with prenatal risk factors for later psychiatric illness^12,26 and with increased risk for developing psychiatric symptoms at 4 years of age²⁷. However, infants with impaired P50 sensory gating have never been followed beyond 4 years of age; thus it remains unclear if infant P50 sensory gating is predictive of later psychopathology or if efforts to alter infant P50 sensory gating will be useful as primary prevention strategies.

The adaptation of auditory P50 sensory gating paradigm for infant study allows exploration of questions related to when during development cerebral inhibition develops and when that development goes awry for individuals vulnerable to later attention-associated neuropsychiatric illnesses. Similar efforts with other physiological tasks, such as mismatch negativity, eye tracking, and prepulse inhibition may offer other windows into early development. It is hoped that the adaptation of tasks for use in early infancy may increase understanding of the developmental time course of these disorders as well as suggest novel primary prevention strategies¹⁷.