Thalamus-Targeted Drugs Could Treat Schizophrenia

Three groups of collaborating researchers discovered that the thalamus, an egg-shaped structure in the brain, is involved with thinking circuitry. Previously, the structure was thought to only relay information, but has been observed to help distinguish categories and keep thoughts in the mind, according to new study published by Nature and Nature Neuroscience.

The authors manipulated neurons in the thalamus to control an animal’s ability to remember how to receive a reward. These findings could lead to a targeted treatment to reduce cognitive problems associated with various psychiatric disorders, such as schizophrenia.

“If the brain works like an orchestra, our results suggest the thalamus may be its conductor,” said researcher Michael Halassa, MD, PhD. “It helps ensembles play in-sync by boosting their functional connectivity.”

Previous studies have suggested that the thalamus had a relay-like role in the brain due to its connections to portions of the brain that process sensory input. However, the authors of the new study state that the thalamus has connections to many other parts of the brain.

Specifically, the authors investigated the circuit that connects the mediodorsal thalamus with the prefrontal cortex (PFC), which controls thinking and decision making. Brain imaging has suggested that patients with schizophrenia often have decreased connectivity in this circuit.

The authors discovered that neurons in the thalamus and PFC communicated back and forth in mice, according to the study. Then, they monitored neural activity in mice performing an activity requiring working memory — the mice were tasked to follow cues to determine which door had a reward behind it.

Interestingly, when the neuronal activity in the thalamus was suppressed, mice were unable to choose the correct door, but when neuronal activity was stimulated, the mice had improved performance, according to the study.

These findings confirm previous notions about the role for the thalamus and also demonstrated a specific role in maintaining information in working memory.

The authors noted that sets of PFC neurons held memory regarding information about the correct door choice. The thalamus did not relay this information, but increased functional connectivity of PFC neurons, which was deemed vital for sustaining memory of the category, according to the study.

“Our study may have uncovered the key circuit elements underlying how the brain represents categories,” Dr Halassa said.

The second group of investigators found similar results when testing mice’s ability to find a reward in a maze. The authors also discovered the differentiated roles for subgroups of PFC neurons and how they communicate with the hippocampus.

They found that thalamus input to the PFC maintained working memory by stabilizing activity during a delay before the mice received the reward. Signals from the PFC to the thalamus sustained memory retrieval and action, according to the study.

These findings confirm that input from the hippocampus was required to encode the reward location in PFC neurons, according to the study.

“Strikingly, we found 2 separate populations of neurons in the PFC. One encoded for spatial location and required hippocampal input; the other was active during memory maintenance and required thalamic input,” said researcher Joshua Gordon, MD. “Our findings should have translational relevance, particularly to schizophrenia. Further study of how this circuit might go awry and cause working memory deficits holds promise for improved diagnosis and more targeted therapeutic approaches.”

The third group of investigators observed that the thalamus plays a role in short-term memory as well. The authors found that the thalamus cooperates with the cortex through bi-directional interactions, according to the study.

Before the mice received the reward, they needed to remember where to move after a delay. The authors found that the thalamus was communicating with the motor cortex when the mice were planning to move.

There was electrical activity in both structures during this time, which indicates that they work together to sustain information predicting the movement of the mice. An additional analysis revealed that the activity of the cortex and thalamus was dependent on one another, according to the study.

“Our results show that cortex circuits alone can’t sustain the neural activity required to prepare for movement,” said researcher Charles Gerfen, PhD. “It also requires reciprocal participation across multiple brain areas, including the thalamus as a critical hub in the circuit.”