Could Behavioral or Pharmacological Interventions for Parvalbumin Interneurons Be Effective?

Behavioral-and-Drug-Interventions
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Researchers looked at whether parvalbumin interneurons could have a mediating role in psychiatric illnesses and if certain pharmacological or behavioral interventions may be effective at targeting these interneurons.

Parvalbumin (PV) interneurons could have a mediating role in psychiatric illnesses, such as schizophrenia, and certain pharmacological or behavioral interventions may be effective at targeting these interneurons. The evidence of this perspective was discussed in a review published in the Journal of Neuropsychiatry and Clinical Neuroscience.

PV interneurons modulate important aspects of motor skills and habitual learning by generating gamma frequency which inhibits cortical pyramidal neurons that project to striatal neurons. These interneurons are highly vulnerable to stressors and require high energy to support metabolic activity.

The PV protein is a calcium-binding protein involved in the signal transduction process in excitable tissues such as muscles and neurons. These proteins are expressed in chandelier and basket cells, which are fast-spiking neurons found in the cortex and striatum. After firing, they cover all nearby pyramidal cells with a densely homogenous matrix, giving them an unparalleled ability to regulate pyramidal neurons through perisomatic inhibition.

Growing evidence supports that appropriate behavioral responses rely on PV interneurons by regulating pyramidal neuronal activity.

In 2003, the first evidence was published indicating that gamma oscillations were responsible for perceptual processes of cognition and information processing among patients with epilepsy.

For patients with epilepsy, schizophrenia, Alzheimer disease, autism spectrum disorder, and bipolar disorder, there is evidence that fast-spiking PV interneurons are significantly depleted in the prefrontal cortex. These brain changes have been associated with social withdrawal, deficits in working memory, and diminished cognitive flexibility.

Stress has been found to inactivate PV interneurons and promote the loss of the intraneuronal spiny dendritic processes. This process can be affected by pharmacogenetic interventions. For example, ketamine has been found to prevent the spiny dendritic loss caused by stress and increase the activity of PV interneurons.

There is also evidence to support behavioral interventions for targeting PV interneurons. Some studies have found that meditative mindfulness might affect central and parietal gamma patterns compared with a mindless task. Another study found that experienced meditators (>10 years of daily practice) were associated with increased occipital gamma patterns. These observations have led to the hypothesis that a meditative state may allow for individuals to increase their neuroplasticity by synchronizing their alpha, theta, and gamma waves.

Additional research is needed in order to disentangle the complex interaction between psychological illness and brain morphology and the interaction with PV interneuron-targeted pharmacotherapies or behavioral interventions.

“In summary, PV interneuron-generated gamma oscillation may function in conscious perception, memory-based cognitive functions, and attentive processing of information. […] This article is focused primarily on gamma frequency oscillation, which is generated by PV interneurons, to develop insight and perspective into the role of PV interneurons in meditation. This article also points to new and emerging directions that address whether this role of PV interneurons in meditation extends to a beneficial, and potentially therapeutic, role in the treatment of common psychiatric disorders, including schizophrenia,” concluded the review authors.

Reference

Thippaiah SM, Pradhan B, Voyiaziakis E, et al. Possible role of parvalbumin interneurons in meditation and psychiatric illness. J Neuropsychiatry Clin Neurosci. 2022;appineuropsych21050136. doi:10.1176/appi.neuropsych.21050136