New Study Shows How Tweaking The Brain Can Reduce Signs Of Autism

Researchers have discovered that a brain region called the thalamic reticular nucleus may play a key role in autism. In mice with genetic alterations linked to autism, this region showed excessive activity, which was linked to seizures, sleep difficulties, and repetitive behaviors. When scientists reduced this activity with medications or special techniques, symptoms improved. This suggests that controlling this part of the brain may offer a new avenue for future treatments.

Autism Spectrum Disorders are brain developmental conditions that typically manifest in childhood. People with autism may have difficulty interacting socially, exhibit repetitive behaviors, and develop associated problems such as sleep disturbances, hypersensitivity to sounds, lights, and textures, and in some cases, seizures. Scientists have long sought to understand how different brain regions and their circuits contribute to these symptoms.

Among these regions, an area called the thalamocortical circuit has received considerable attention. This circuit connects the thalamus, a structure in the center of the brain responsible for organizing and transmitting sensory information, to the cortex, where this information is processed.

Within the thalamus, there is a section called the thalamic reticular nucleus, which acts as a "gatekeeper": it regulates incoming and outgoing sensory information, in addition to influencing sleep, attention, and even the onset of seizures.

When this area malfunctions, it can lead to disorganized brain rhythms, which have been linked to several neurological conditions, such as attention deficit, schizophrenia, and depression.

To better understand the relationship between the thalamic reticular nucleus and autism, researchers used mice genetically modified to lack a gene called Cntnap2. This gene has already been linked to autism in humans, and mice lacking it develop behaviors similar to those seen in people with autism, such as hyperactivity, difficulty sleeping, seizures, and sensory perception problems.

In the study, scientists at Stanford University, USA, analyzed how neurons in the thalamic reticular nucleus functioned in these mice. To do this, they used electrophysiological recordings, which are techniques that measure the electrical activity of neurons, allowing them to determine whether they are firing normally or excessively.

They also used in vivo fiber photometry, a method that allows real-time observation of the activity of groups of neurons while the animal is awake and behaving.

The results showed that neurons in the thalamic reticular nucleus of these mice were overactive, firing in more frequent bursts and exhibiting abnormal rhythms in the thalamus. This was directly associated with autism-like behaviors, such as repetitive movements and a greater tendency to seizures.

To confirm whether this hyperactivity was actually causing the behavioral problems, the researchers tested ways to reduce the activity of these neurons. They used two strategies: the first was a drug called Z944, which blocks calcium channels responsible for this hyperexcitability; the second was a technique called chemogenetics, which allows the activity of specific neurons to be controlled through artificial receptors activated by safe drugs.

In both cases, when the activity of the thalamic reticular nucleus was reduced, the mice showed significant improvements in autism-related behaviors.

In conclusion, the study showed that overactivity of the thalamic reticular nucleus may be one of the mechanisms contributing to autism symptoms. This paves the way for the development of new treatments that do not act on the entire brain, but rather target specific circuits.

Future research still needs to verify whether this same mechanism is present in other types of autism with different genetic origins, but the results point to the thalamic reticular nucleus as a promising target for more effective therapies.

READ MORE:

Reticular thalamic hyperexcitability drives autism spectrum disorder behaviors in the Cntnap2 model of autism

Sung-Soo Jang, Fuga Takahashi, and John R. Huguenard

Science Advances. Vol 11, Issue 34. 20 August 2025

DOI: 10.1126/sciadv.adw4682

Abstract: 

Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by social deficits, repetitive behaviors, and comorbidities such as sensory abnormalities, sleep disturbances, and seizures. Although thalamocortical circuit dysfunction has been implicated in these symptoms, its precise roles in ASD pathophysiology remain poorly understood. Here, we examine the specific contribution of the reticular thalamic nucleus (RT), a key modulator of thalamocortical activity, to ASD-related behavioral deficits using a Cntnap2 knockout mouse model. Cntnap2−/− mice displayed increased seizure susceptibility, locomotor activity, and repetitive behaviors. Electrophysiological recordings revealed enhanced intrathalamic oscillations and burst firing in RT neurons, accompanied by elevated T-type calcium currents. In vivo fiber photometry confirmed behavior-associated increases in RT population activity. Notably, pharmacological and chemogenetic suppression of RT excitability via Z944, a T-type calcium channel blocker, and via C21 activation of the inhibitory DREADD hM4Di significantly improved ASD-related behaviors. These findings identify RT hyperexcitability as a mechanistic driver of ASD and highlight RT as a potential therapeutic target.