To investigate the role of midline thalamus and its communication with other brain regions we used mice to record brain activity at multiple brain areas at the same time, while mice were exploring a familiar environment for food, running on a wheel, or just sleeping. During sleep the brain is detached from its environment and generates its own internal activity patterns with minimal sensory influence. Therefore, sleep can be considered as a default state of the brain where one can investigate the basic functional connections and relationships between brain areas.
It is technically challenging to monitor neuronal activity at multiple locations of the brain in a freely moving mouse. We designed a recording configuration, where we implanted three electrode arrays into the brain in order to monitor neuronal electrical activity within the midline thalamus and in two other connected brain areas relevant for memory formation and for organizing behavior: the hippocampus and the prefrontal cortex, respectively. The challenge, on the one hand, was to miniaturize the holding components of electrode arrays to be able to fit them onto the small skull of a mouse. For that we used the most sophisticated commercially available electrode arrays and designed high quality 3D printed materials to position them. On the other hand, we needed to discriminate midline thalamic neurons from surrounding neurons. Midline thalamic neurons express a protein, called Calretinin, which neighboring neurons lack. Taking advantage of advanced genetic techniques (transgenic mice, optogenetics), we were able to turn these Calretinin containing neurons light sensitive: by shining brief light pulses into the thalamus, we were able to temporarily activate these neurons, hence we could tell which neurons belonged to the midline thalamus and which didn’t.
The brain generates different electrical activity patterns in different brain states (like slow oscillation during sleep but much faster oscillations during wakefulness), which suggests that the brain performs different computations in these states. Once we identified midline thalamic neurons with our electrodes, we monitored their activity in various brain states and across multiple behavioral conditions. We were curious how different the activity of midline thalamic neurons was during sleep and during exploration and how their activity coupled to the neuronal activity of the cortex and hippocampus. Our experiments revealed a strongly interconnected tripartite circuit, where the midline thalamic activity is strongly coupled to the cortical and hippocampal activity during sleep and wakefulness. While our experiments are still ongoing, our results clearly suggest that the midline thalamus is extensively but differentially communicate with the hippocampus and cortex in multiple brain and behavioral states. We presented our results in several international conferences both within Europe and in the United States.
