Research

The main focus of the lab in the first 5 years is the work proposed in our ERC grant. The three objectives/projects are described below.

Objective 1: Determine the impact of context on innate behaviours.

In this project, we aim to understand how contextual information can change innate reactions to visual stimuli. To test this, we let rodents move freely in a box and show them visual stimuli that mimick for example an approaching threat while we film their reactions. Through controlled changes of different contextual parameters, we test if and how the reaction (= output) to the very same stimulus (= input) can be modulated. Our main question here is: Is there a defined set of possible context-dependent modifications in innate behaviour and are they the same for dfferent types of contexts and species from different habitats? Our lab focuses on 3 different contexts:

1) Ambient light: An external and transient change in context with very important implications and meanings for all mammals. We believe that ambient light is of particular interest because it can signify short time periods (changes in light during the day), longer time periods (seasonal changes in light), weather conditions which may change how easily detectable an individual is or whether their predators are actively searching for food, but it can also be actively changed through movement from and into differently lit spaces.

2) Time of day (circadian rhtythm): Circadian rhtythm is an internal transient context. We choose to study how the time of day affects innate behaviours because of two main reasons. First, it allows us to disentangle impacts of time and light by investigating behaviours at different times of the day with matching or non-matching light conditions. Second, different times of the day are linked to internal hormonal states but also to expectations of how likely it is to find food, be detected by a predator etc.

3) Ecological niche (evolution): Changes in ecological niches are an external contextual factor that can lead to permanent modulation of innate behaviors through genetically encoded differences in the underlying circuit. We want to know whether such permanent adaptation leads to similar types of behaviour changes as transient changes in context.

Objective 2: Determine the impact of context on neural circuitry.

In this second project, we will investigate the neural circuits that mediate innate behviours and how the encoding of visual stimuli and motor output changes in a context-specific way. To this end, we perform electrophsyiological recordings and calcium imaging in the circuits of the superior colliculus which are known to mediate different types of innate reactions such as escape and freezing. Again, rodents will be exposed to visual stimuli under different contexts and we will measure how different circuits encode the stimuli and correlate with the observed motor reaction. In a second step, we will investigate selected inputs to the superior colliculus which are likely encoding information about ambient light and time of day, and which hence might be the source of modulatory inputs to those behaviour-driving circuits. These experiments will address threebig questions: (1) What aspects of visual encoding can be modified by context? (2) Are changes in behaviour type and kinetics encoded in the early stages of visuo-motor circuits? (3) Are context-specific changes in encoding cell-type and/or circuit and/or species specific?

Objective 3: Dissect the mechanisms of neural and behavioural adjustments to context.

In the final step of the ERC proposal, we want to understand through which mechanisms brain areas that encode contextual information can impact behaviour-driving circuits. Here, we will use modulatory tools (siRNA, chemogenetics, optogenetics, application of neuromodulators) to probe whether the identified modulatory inputs are sufficient and necessary for contextual adaptation, and to understand through which mechanisms (spiking, neuromodulation) this adaptation is mediated. This will reveal: (1) whether the inputs of context-encoding brain areas is sufficient to produce context-specific behaviour. And (2) whether these mechanisms are conserved across species.

Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. ERC, FLEXIN, 101075848.

In this collaborative project together with the Legname Lab at SISSA, we want to understand the impact of having no prion protein expression on behaviour and neural circuit function. The project was initiated by Lorenza and is now executed by Camilla and Lucia.

Background: Prions, misfolded versions of the prion protein, can lead to severe and fatal diseases in mammals, including in humans (where it leads to Creutzfeldt–Jakob disease). Any potentially promising treatment of prion protein related diseases entails removal of all prion protein, not only the misfolded one. However, the role of the normal prion protein and the consequences of removing it completely remain unclear. Multiple mouse lines that lack prion protein have been developed, most recently the most "clean" line ZH3. Such mouse lines allow us to investigate what effect the lack of prion protein has on the brain.

Objective 1: Determine the impact of prion protein knockout on innate behaviours.

Previous litarature suggest that there might be an impact of prion protein knockout on fear-like behaviours. However, the studies haven't been very conclusive and were performed in the older mouse models. Here we aim to compare the innate foraging and aversive behaviours of ZH3-KO (mice lacking prion protein) and their healthy littermates ZH3-WT. We use spontaneous foraging in open field and visually induced aversive reactions as a read-out. In a second set of experiments, we study how the two genotypes react to head-fixation and whether they are able to habituate to new situations.

Objective 2: Determine the impact of prion protein knockout on neural function.

Prion proteins are expressed in the brain and play a role in many aspects of neurogenesis and neural network formation. It is hence conceivable that the lack of this protein will lead to brain alterations. Data from our collaborators on in-vitro neuron cultures indeed suggests some rather strong effects. Here we aim to understand whether we see similar effects on the intact brain in-vivo, and specifically, if we see alterations in the circuits that mediate the innate aversive behaviours tested in Objective 1. To perform these experiments we use Neuropixels probes.