Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - SensoNMDA (Impact of NMDA receptor diversity in sensory information processing)

Teaser

The human brain is a remarkable computation device whose function relies mostly in the activity of networks of neurons communicating with each other via specialized connections denominated synapses. The presence of an extremely elevated number of neurons and a complex...

Summary

The human brain is a remarkable computation device whose function relies mostly in the activity of networks of neurons communicating with each other via specialized connections denominated synapses. The presence of an extremely elevated number of neurons and a complex connectivity diagram among the different cellular elements are clear contributors to such unique functional capabilities. However, is now particularly obvious that the functional properties of synapses are not uniform but rather variable across synapses in the brain. The functional consequence of such diversity is not clear but is thought to increase computational power.
We are presently investigating how diversity in synaptic function contributes to information processing in the primary somatosensory cortex. Understanding the cellular mechanisms involved in information process by the brain is a fundamental question in neuroscience and a better knowledge of the human brain is expected to help in the development of new therapeutical approaches to correct brain dysfunction associated with neurological diseases and disorders.
We have focused our attention in the glutamate receptor NMDA, whose activity is essential for correct brain function and has been implicated in key brain functions like learning and memory. We have observed that the density and biophysical properties of synaptic NMDAR are particular variable among local GABAergic interneurons in primary somatosensory cortex and we are presently carrying in vivo experiemnts to investigate the impact of such diversity in the computation of sensory information.

Work performed

To tackle the proposed objectives, we have been using an array of genetic, optogenetic and pharmacological tools in combination with imaging and electrophysiological approaches. Specifically, we have identified zinc as a selective modulator of synaptic plasticity and dendritic non-linearities in the primary somatosensory cortex through its actions on synaptic NMDARs. We were also able to observe that neocortical interneurons express functional NMDARs with unusual biophysical properties. Presently we are investigating the in vivo relevance of these two findings. For that we were able to setup in vivo calcium imaging of defined cell populations in awake moving head-restraint animals. Preliminary results suggest that NMDARs play an important role in the computation of sensory information in the primary somatosensory cortex.

Final results

The new cellular elements now reported reveal previously unknown modulatory systems in cortical function. We expect that by the end of the project to have identified a new pathway by which NMDARs and endogenous modulators of NMDAR function (zinc) impacts the process of sensory information.