Spühler I, Conley M, Scheffold F and Specher SG 

Super resolution imaging of genetically labelled synapses in Drosophila brain tissue

Frontiers in Cellular Neuroscience, April 2016


Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labeled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation.



Masek P, Worden K, Aso Y, Rubin GM and Keene AC

A dopamine-modulated neural circuit regulating aversive taste memory in Drosophila.

Current Biology 2015, June 1;25(11):1535-41. 

Author summary:

Taste memories allow animals to modulate feeding behavior in accordance with past experience and avoid the consumption of potentially harmful food . We have developed a single-fly taste memory assay to functionally interrogate the neural circuitry encoding taste memories. Here, we screen a collection of Split-GAL4 lines that label small populations of neurons associated with the fly memory center-the mushroom bodies (MBs). Genetic silencing of PPL1 dopamine neurons disrupts conditioned, but not naive, feeding behavior, suggesting these neurons are selectively involved in the conditioned taste response. We identify two PPL1 subpopulations that innervate the MB α lobe and are essential for aversive taste memory. Thermogenetic activation of these dopamine neurons during training induces memory, indicating these neurons are sufficient for the reinforcing properties of bitter tastant to the MBs. Silencing of either the intrinsic MB neurons or the output neurons from the α lobe disrupts taste conditioning. Thermogenetic manipulation of these output neurons alters naive feeding response, suggesting that dopamine neurons modulate the threshold of response to appetitive tastants. Taken together, these findings detail a neural mechanism underlying the formation of taste memory and provide a functional model for dopamine-dependent plasticity in Drosophila.



Diegelmann S and Sprecher SG .

An epigenetic way to forget those painful memories

Trends in Neurosciences. 2014 May;37(5) 245-6



Traumatic experience can be overwhelming, thus erasing associated memories is desirable. Although exposure-based and reconsolidation methods have been developed for recently acquired associations, treatments to modify more distant memories are rare. Focusing on HDAC2 inhibition during reconsolidation, Gräff and colleagues recently demonstrated an epigenetic means to attenuate remote fear memory.



Brea J, Urbanczik R and Senn W.

A normative theory of forgetting: lessons from the fruit fly.

 PLoS Comput Biol. 2014 Jun 5;10(6)


Author Summary:

The dominant perception of forgetting in science and society is that it is a nuisance in achieving better memory performance. However, recent experiments in the fruit fly show that the forgetting rate is biochemically adapted to the environment, raising doubts that slower forgetting per se is a desirable feature. Here we show that, in fact, optimal behavior in a stochastically changing environment requires a forgetting rate that is adapted to the time constant of the changes. The fruit fly behavior is compatible with the classical optimality criterion of choosing actions that maximize future rewards. A consequence of future reward maximization is that negative experiences that lead to timid behavior should be quickly forgotten in order to not miss rewarding opportunities. In economics this is called ‘‘minimization of opportunity costs’’, and the fruit fly seems to care about it: punishment is forgotten faster than reward. Forgetting as a trait of optimality can further explain the different memory performances for multiple training sessions with varying inter-session intervals, as observed in a wide range of species from flies to humans. These aspects suggest to view forgetting as a dimension of adaptive behavior that is tuned to the environment to maximize subjective benefits.