Autism Behaviors Reversed In Mice Using Experimental Seizure Drug
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Stanford scientists find a brain region that can control symptoms
In a word
- Stanford researchers found that hyperactive neurons in the reticular thalamic nucleus lead to autistic type behaviors in mice.
- To calm these neurons with Z944 genetic tools (a blocking channel blocker) or DREADD has restored normal behavior.
- Treated mice showed improved social interaction, reduced repetitive grooming and standardized activity.
- Although promising, these results come only from mouse studies; Human trials are necessary before any treatment application.
Stanford, California – Scientists at the University of Stanford have identified a specific brain region which seems to stimulate the symptoms of basic autism in mice and successfully improved these behaviors using targeted treatments. The breakthrough focuses on hyperactive neurons deep in the brain which serves as guards for sensory information, controlling signals reaching conscious consciousness.
The results, published in Scientific advancescome from mouse studies, from a standard model in autism research, and other works are necessary before testing in humans. However, the results point to potential therapies that can approach the biological foundations of autism rather than simply manage symptoms.
Hyperactive brain cells disrupt normal function
The problem comes from a brain structure called Reticular thalamic nucleuswhich acts as a traffic control system for sensory information. In healthy brains, this region determines what sensory signals (sounds, views and keys) guarantee the attention of the upper brain areas. In mice of the autistic model, however, these neurons fired in rapid and excessive bursts that blurred normal brain communication.
Stanford researchers studied mice designed to miss CNTNAP2, a gene strongly linked to autism in humans. These mice classic autism type features, including social avoidance other mice, repetitive grooming, hyperactivity and Increase in crisis sensitivity. Brain examinations revealed that the reticular neurons of the Thalamic nucleus pulled much more frequently than normal.
Scientists have drawn this hyperactivity to hyperactive calcium channels, proteins that regulate the way in which neurons communicate. In mice of the autistic model, these type T calcium channels have allowed the neurons of burst much more easily, which made it possible to disturb the brain signals that have manifested themselves as behavioral symptoms.
Two treatment methods are promising
The researchers tested whether the reduction in this neural overactivity could restore normal behavior using two different approaches, both of which produced remarkable results.
First of all, they administered Z944, a medication that blocks problematic calcium channels, with mice. Mouses receiving this treatment have shown substantial behavioral improvements, including a decrease in hyperactivity, restored social preferences and a cessation of excessive grooming behaviors. Z944 has already undergone human tests to treat certain types of crises, which could accelerate its potential path to autistic trials.
The second method used advanced genetic tools called DRADDS (designer receptors activated exclusively by designer medicines). Scientists have changed mice so that specific neurons can be checked using technical proteins and corresponding drugs. When they used this technique to calm the activity of the reticular thalamic nucleus, autism type behaviors have once again improved.
More convincing, the researchers have demonstrated the opposite: the artificial increase in activity in these brain cells has developed normal autism type behaviors, in particular a reduced social interaction and an increase in repetitive actions.
Targeting symptoms
Previous research on autism has focused mainly on the outer layer of the brain, where a complex thought occurs. But this study reveals that the behavioral symptoms of autism can actually begin in a much deeper and more primitive brain region that manages basic sensory treatment and attention.
The reticular thalamic nucleus connects to many brain areas involved in sensory treatment, attention and emotional regulation. When it becomes hyperactive, the resulting disturbance simultaneously affects several brain networks, which explains why autism involves such various symptoms affecting social behavior, sensory treatment and repetitive actions.
Most neurons in this brain region produce a protein called parvalbuminWhat previous research has been linked several times to autism. Previous studies have revealed fewer neurons producing parvalbumin in autism models and in the brain tissues of autistic people.
Current autism treatments focus on behavioral interventions and drugs that deal with secondary symptoms such as anxiety or hyperactivity. A treatment targeting calcium type T-type channels could potentially approach the basic characteristics of autism directly by correcting underlying brain dysfunction rather than managing its effects.
The transition from laboratory discovery to human treatment requires additional studies in other autism models and possible human clinical trials. Since Z944 has already been tested in humans for other conditions, this could potentially accelerate the development of specific treatments based on these principles.
If these results ultimately apply to humans, autistic people and their families could one day access more effective treatments that approach the neurobiological foundations of the condition rather than managing symptoms.
Non-liability clause: This study was conducted in mice and does not represent an approved treatment for autism in humans. The results are preliminary and require additional research, including human clinical trials, before any medical demand. Individuals should not interpret this research as medical advice or modify existing treatments without consulting qualified health professionals.
Paper summary
Methodology
The researchers have used Knockout CNTNAP2 mice, which lack a gene strongly associated with autism in humans and display autism type behaviors, in particular hyperactivity, reduced social interaction and repetitive behavior. The team used several experimental approaches: Patch-Clamp recordings with whole cells to measure electrical activity in individual brain cells, fiber photometry to follow neuronal activity in living mice during behaviors, optogenetics to stimulate specific neurons with light and chemigenetics (DRDDS) to activate selectively or selectively inhibit neurons. They carried out behavioral tests, including open field tests for hyperactivity, three -room tests for social preferences, grooming assessments and sensitivity measures to the crisis using electroencephalogram recordings.
Results
The study revealed that neurons in the reticular thalamic nucleus of autistic model mice have shown an increase in bursting of burst and high -type calcium currents compared to normal mice. In vivo recordings have revealed increased neuronal activity during various behaviors, including exposure to light, social interactions and crisis induction. Pharmacological treatment with Z944 (a blocker of calcium channels of type T) and the chemoogenetic removal of the activity of the reticular thalamic nucleus has considerably improved autistic behavior, in particular hyperactivity, social deficits and repetitive grooming. Conversely, the artificial activation of these neurons in normal mice has induced autism type behaviors, demonstrating a causal relationship.
Boundaries
The study has only used male mice because CNTNAP2 female Knock-out mice do not have important behavioral anomalies. Research has focused on a single genetic model of autism, and the results may not become widespread in other forms of the condition. Type-clamp recordings of type T calcium currents represent a technical compromise due to the difficulty of completely isolation of these currents in brain slices. The study did not examine different subpopulations of reticulum of the Thalamic nucleus or evaluated the long-term development effects of interventions.
Financing and disclosure
This research was supported by the SFARI price number 633450 and the NIMH R01 MH121075 subsidy. The authors have not declared any competing interest. All animal procedures have been approved by Stanford’s administrative panel on laboratory animal care and conducted in accordance with the Directives of the National Institutes of Health.
Publication information
The study “Reticular thalamic hyperexcitability leads to autism spectrum disorder behaviors in the CNTNAP2 autism model” was led by Sung-Soo Jang, Fuga Takahashi and John R. Huguard from the Department of Neurology and Neurological Sciences of the Stanford University School of Medicine. It was published in Scientific advancesVolume 11, EADW4682 article number, August 20, 2025.
