Problems being addressed:
The mammalian brain integrates behaviorally relevant sensory information by recruiting large parts of the neocortex to enable precise perception, apt decisions and appropriate actions. However, we still poorly understand which brain regions are activated during specific cognitive functions and how they relate to behavioral parameters. For example, it is unknown which cortical areas maintain short-term memory, or which areas are involved in learning a new task.
Overall objectives:
For the outgoing phase: To study the large-scale cortical dynamics as mice perform a tactile memory task. Specifically, we were interested in finding the cortical locations of sensory integration and especially short-term memory maintenance.
For the return phase: To study the population dynamics in the auditory thalamus during learning of an auditory go/no-go discrimination task.
Importance for society:
This findings highlight the dynamic plasticity of neuronal networks at the mesoscale level, which greatly differs from artificial hard-wired networks. This project expands our understanding of how the healthy brain flexibly maintains memory, and may aid in understanding the disease-related brain. Several neurodegenerative diseases such as Parkinson and Alzheimer are characterized by memory impairment which is one of the most common complaints from patients. The frontoposterior network studied in this project has been linked to neurodegenerative disorders and our work adds on to its role in short-term memory. Having the ability to also manipulate the network is a big advantage that is not enabled in human studies. In addition, we show the complex neuronal dynamics during learning of a new task. Learning involves many cortical areas which eventually leads to a refinement of relevant association cortex that may underlie gaining expertise. The comprehensive understanding of the neuronal correlates of learning may aid in diagnosing and improving subjects with learning disorders, e.g. dyslexia.
Conclusions of the action:
For the outgoing phase: We found multidimensional cortical dynamics involved in both sensory integration and short-term memory and also related strongly to the behavioral parameters of each mouse. Mice either deployed an active or passive strategy. Independent of strategy, whisker-related posterior areas encoded choice early after touch. During the delay, in contrast, persistent cortical activity was located medio-frontally in active trials but in a lateral posterior area in passive trials. Perturbing these areas impaired performance for the associated strategy and also provoked strategy switches. Thus, depending on behavioral strategy, cortical activity is routed differentially to hold information either frontally or posteriorly before converging to similar action.
For the return phase: We found that thalamic responses in expert mice encoded the choice of the mouse, as we could rapidly discriminate between hit and miss trials. In addition, we observed opposite effects on the go and no-go responses. In recordings sites preferring the ‘go’ sounds, responses to ‘go’ on hit trials increased. In recordings sites preferring the ‘no-go’ sounds, responses to ‘no-go’ sounds decreased. There was a strong correlation between the time in which the mouse crossed behavioral threshold to expert level and the time in which thalamus responses displayed the strongest modulation (either go enhancement or no-go suppression). These results show that the auditory thalamus encodes task- and learning-related information.