summary: Researchers have explored potential treatments for neuropsychiatric disorders such as schizophrenia and autism, which act during critical periods of brain development.
They specifically targeted underperforming dopamine neurons, which connect to the frontal cortex and are essential for cognitive processing and decision-making. By stimulating these neurons in mice during puberty, long-lasting changes were observed that rescued structural defects in the brain that cause persistent symptoms.
These findings suggest that interventions during development may alter the course of these disorders.
Important facts:
- The development of neuropsychiatric disorders is often correlated with dysfunction of the dopamine system, which becomes apparent during adolescence.
- Stimulating underperforming dopamine neurons in mice during puberty produced long-lasting changes that corrected structural defects in the brain.
- Targeting these critical periods of development may offer a way to alter the progression of neuropsychiatric disorders such as schizophrenia and autism.
sauce: University of Rochester
The brain undergoes continuous changes during childhood and adolescence. The onset of neuropsychiatric disorders such as schizophrenia often begins in young adulthood.
Dysfunction of the dopamine system required for cognitive processing and decision-making begins at this point in development.
Researchers at the University of Rochester Del Monte Neuroscience Institute have found a potential for treating neuropsychiatric disorders such as schizophrenia and autism during development, which can affect brain circuits well into adulthood. approaching discovery of a target with
“Brain development is a long process, and many nervous systems have critical periods, when areas of the brain are malleable and undergo final stages of maturation,” said the University of Rochester Medical Center. Dr. Leanne Stowell, a postdoctoral fellow in Wang’s lab, said.Co-first author of a study published in the journal e-life.
“Identifying these periods may allow us to target interventions to these periods and alter the course of the disease by rescuing the structural and behavioral deficits caused by these diseases.” there is.”
The researchers targeted neurons with underperforming dopaminergic systems that lead to the frontal lobes of mice. This circuit is essential for advanced cognitive processing and decision making.
They found that stimulating the cells that supply dopamine to the frontal cortex strengthened this circuit and rescued structural defects in the brain that caused long-term symptoms.
Previous research in the Wang lab found that this particular part of the dopamine system is flexible in adolescent brains, but not in adults. In this latest study, we exploited this system’s window of plasticity as an opportunity for therapeutic intervention.
“These findings suggest that increasing the activity of dopaminergic circuits during adolescence can remedy pre-existing defects in the circuits, and because these changes persist into adulthood, this effect may be long-lasting. It suggests that,” Stowell said.
“If we can target the right regions during development and understand the signals that are being generated, we will be able to develop therapies that alter the course of these brain diseases.”
The study is led by lead author Dr. Quan Hong Wang of the University of Rochester Medical Center. Co-lead authors include his Surjeet Mastwal and Xinjian Li from the National Institute of Mental Health. Additional authors include Wenyu Zhang from the University of Rochester Medical Center, Matthew Manion from the National Institute of Mental Health, and Nam-Shik Kim, Ki-jun Yuon, Hongjun Song, and Guo-li Ming from the University of Pennsylvania.
Funding: This study was supported by a pilot program at the National Institutes of Health and the Del Monte Neuroscience Institute.
About this mental health and neurodevelopmental research news
author: Kelsey Smith Hejduk
sauce: University of Rochester
contact: Kelsey Smith Hejduk – University of Rochester
image: Image credited to Neuroscience News
Original research: open access.
“Neurostimulation of adolescent dopamine circuits reverses genetic deficits in frontal cortex functionby Leanne Stowell et al. e-life
overview
Neurostimulation of adolescent dopamine circuits reverses genetic deficits in frontal cortex function
Dysfunction of the dopamine system is associated with neuropsychiatric disorders commonly occurring during adolescence.
Psychotic symptoms may be alleviated by antipsychotics, but cognitive symptoms remain unresponsive to such pharmacological treatments, making a new research paradigm to investigate the circuit substrates underlying cognitive deficits very much. is necessary.
Dopaminergic input from the frontal cortex and midbrain is involved in cognitive function and undergoes maturational changes during puberty.
Here we used mice carrying the mutation. arc again DISC1 Genes to model dopamine circuit defects in the middle frontal lobe and test circuit-based neurostimulation strategies to restore cognitive function.
We found that in a memory-induced spatial navigation task, frontal cortical neurons were coordinately activated at the point of decision-making in wild-type, but not wild-type. arc mutant mouse.
Chemogenetic stimulation of midbrain dopamine neurons in limited adolescence or optogenetic stimulation of frontal cortical dopamine axons is based on midfrontal innervation, task-tailored neuronal activity, and memory in adulthood. Consistently reversed genetic deficiencies in decision making.
Furthermore, stimulation of adolescent dopamine neurons also reversed midfrontal circuits and cognitive deficits. DISC1 mutant mouse.
Our findings reveal alterations in common midfrontal circuits underlying cognitive deficits caused by two different genes and the feasibility of adolescent neurostimulation to reverse these circuit and behavioral deficits. demonstrate gender.
These results may suggest developmental windows and circuit targets for treating cognitive deficits in neurodevelopmental disorders.
