Featured Lendület Member: László Acsády
The thalamus is one of the most underestimated brain areas. According to the classical view, its only job is to act as a switching station between the cerebral cortex and stimuli from the outside world. However, László Acsády, head of the MTA-KOKI Momentum Thalamus Research Group and deputy director of the HUN-REN Institute of Experimental Medicine (KOKI), and his colleagues have shown in recent decades that this view could not be further from the truth. Indeed, the complex communication between the cortex and the thalamus and the processing that takes place in the thalamic cells prove that this brain area plays an active role in brain function. His brain research team can now continue their research with funding from the Momentum Programme.
The research of Acsády’s Momentum research group reveals the diversity of communication between the cerebral cortex and the thalamus. The human cerebral cortex is one of the most complex organisational structures in the known world. But what is less well known is that no direct connection between the cerebral cortex and the outside world developed during evolution.
László Acsády Fotó: mta.hu / Szigeti TamásOne aim: to study the connections from the cerebral cortex to the thalamus
The thalamus provides this connection: it makes information from the outside world and other areas of the brain available to the cerebral cortex. With the exception of smell, all fast-stimulating and inhibitory information must pass through the thalamus before reaching the cerebral cortex. Whether it is a change in internal state, a command to move, a stimulus from a visual image or any other information, the thalamus plays a central role in its rapid transmission.
Contrary to classical ideas about the thalamus, we now know that this area of the brain is not just a passive “switching relay function,” but that there is a two-way communication between it and the cerebral cortex. All regions of the cerebral cortex have a back-and-forth relationship with the thalamus. “Therefore, brain function can actually be considered as a continuous corticothalamic interaction. This interaction is occasionally altered by changes in the external world or internal states,” says Acsády. “Perception, thinking and planning also emerge from processes triggered by the “disruption” of spontaneous thalamic-cerebral cortex interaction. The connections from the thalamus to the cerebral cortex have been extensively studied. In comparison, surprisingly little attention has been paid to the connections from the cerebral cortex to the thalamus. This is therefore one of the main goals of our Momentum research group.”
How do sensory cortices “talk”?
The reason for the scant study of the pathways from the cerebral cortex to the thalamus is that, according to the traditional view, there are no “important” processes in the thalamus, and all processing, from learning to perception, takes place in the cerebral cortex. However, according to Acsády, this is clearly a misconception: mapping the connections from the cerebral cortex to the thalamus is just as important in terms of understanding brain processes. In addition, bidirectional thalamic-cortical connections are equally important in diseases. While in a healthy nervous system, precisely defined rhythms regulate communication between the thalamus and the cerebral cortex, in the case of disease, abnormal rhythms appear and disrupt healthy functioning. This is what happens in epilepsy, Parkinson’s disease and many other chronic neurological diseases.
Since the time of János Szentágothai, we have imagined brain structures as a modular organisation, that is, the cerebral cortex also consisting of well-defined modules and columns. The modules are made up of many different types of cells, between which incredibly complex connections are made, but the logic of the modules’ construction is the same. Thus, for example, a module in the visual cortex operates on similar principles to the cortical modules in the frontal lobe, although the functions of the two regions are quite different. This phenomenon is also linked to the general question posed by the Momentum Research Group.
“Our research is trying to answer the question of
whether sensory cortices talk to the thalamus in the same way as frontal cortices.
That is, whether the structural and functional principles of communication are the same,” says the team leader. “If the connections of the two brain regions with the thalamus were found to be different, this would also suggest that the brain processes underlying neurological diseases affecting the frontal and sensory cortex are also different.”
Integration of various types of information
The experimental arm of the research programme poses great challenges to the researchers, which is why the project has many legs to stand on. A number of anatomical and physiological experiments are being carried out on genetically modified mice, but primate and human samples are also available. Thus, if any structural or functional trait is discovered in the rodent model, it can be verified in both the primate and human brain. Using state-of-the-art techniques, they can mark the pathways between the cerebral cortex and the thalamus in a cell-type-specific way and measure their activity and their effects on the thalamus. In this way they can compare the structure and function of pathways originating in the sensory and frontal cortex. The experiments will use the most advanced microscopic techniques (electron, light and super-resolution microscopy). They can track the influence of the cerebral cortex on the activity of neurons in the thalamus in living animals, and thus compare the activity of areas receiving input from different cortical areas. The team also conduct behavioural experiments. They will selectively disrupt certain corticothalamic pathways (from the cerebral cortex to the thalamus) and investigate how this interference affects an animal’s behaviour.
Research on the thalamus has been ongoing at the Institute of Experimental Medicine for decades, and the team has already produced a number of results showing that, in the words of Acsády, “corticothalamic communication between the sensory and frontal cortices and the thalamus is fundamentally different”. The structure of the pathways is different, the effects of postsynaptic cells are different, and the plasticity of the pathways is probably different. If it can be shown in the near future that one pathway is more prone to altering the strength of connections (i.e. more plastic) than the other, this will be a key to understanding why one pathway malfunctions and the other does not in pathological situations.
According to the research team leader, it is becoming increasingly clear that the cells of the thalamus do not only receive input from a single location, which they only have to transmit, but also that a wide range of information is integrated in them. This subcortical integration transforms the signal for the cortex so that it becomes interpretable for higher brain areas. In this way, the signal – and thus the cerebral cortex – is enriched with new information that would otherwise be inaccessible to it.
The successful implementation of this programme will fundamentally change our views on the role of the thalamus in cortical communication.