Research

How are memories encoded in the brain? How do the different forms of memory interact?

The major challenge faced by neuroscientists studying memory is to define the links between the various levels of brain organization. Powerful molecular genetics tools available in drosophila, along with the properties of its highly organized brain, make it a model of choice for such an integrated analysis.

Our laboratory is engaged in top-down approach to unravel some of the general mechanisms involved in associative learning and memory.

To study aversive memory we use conditioning protocols during which drosophila associates an odor with electric shocks. Intensive conditioning with a rest interval between the stimulus presentations (spaced conditioning) leads to the formation of aversive long-term memory (LTM).

We also study appetitive memory, which forms in starved flies after odorant and sugar presentation.

Our team has made major discoveries on the dynamics of memory phases in drosophila in the past two decades. Recently, neurons that allow the formation, consolidation or retrieval of the different memory phases have been systematically characterized in drosophila, and our team has played an important role in that process.

We now focus onto two original questions, the analysis of the links between energy metabolism and memory, and the study of the role of APP-related pathways in learning and memory.

The brain is the central regulator of energy homeostasis, and it prioritizes its own supply over peripheral organs.

Intriguingly, a recent study rom our team provides novel evidence that the brain is also able to down-regulate its own activity under energy shortage conditions. Specifically, we showed that energetically costly aversive LTM is inhibited in starved flies to favor survival (Plaçais and Preat 2013).

This brought us to study the interplay between memory formation and brain energy status. We follow an integrated approach to answer the following questions:

• • how is memory dynamics modified by brain energetic status?
  • what are the neuronal circuits that signal the energy level to the olfactory memory center, and how is their activity regulated?
  • what are the molecular mechanisms that underlie the interaction between the energy level and memory formation?
  • what is the energetic cost of LTM formation?
  • how do the neuronal and glial networks interact to manage the energy fluxes underlying memory formation?

We use drosophila to study some aspects of Alzheimer’s disease (AD).

While the main hypothesis for AD pathology centers on the amyloid peptide, generated by proteolytic processing of amyloid precursor protein (APP), little is known about the physiological function of APP and its derivatives in the adult brain.

To gain information on the early stages of AD we think it is essential to better understand the physiological role of the molecular actors of the APP pathway in brain plasticity and memory.

We studied the role of the drosophila ortholog APPL, and we showed that APPL-loss of function in the adult mushroom body affects LTM formation (Goguel et al. 2011).

These data support the hypothesis that disruption of normal APP function may contribute to early AD cognitive impairment.

We currently analyze in details the physiological implication of APPL protein in memory processing, and study several proteins that interact with APPL or its derivatives.