The newly established Silva lab is seeking a Postdoctoral Fellow to study midline thalamic circuits in fear memory and fear extinction in the mouse. The Silva lab combines whole-brain functional tracing, chemogenetics, optogenetics and in vivo fiber photometry to investigate thalamic circuits involved in emotional regulation. We recently discovered that the nucleus reuniens of the thalamus mediates extinction of remote (older than 30 days) fear memories (Silva et al. Nat. Neurosci. 2021) and we are currently working to unravel its functional upstream and downstream partners. The successful candidate will design and implement experiments to elucidate and characterize the NRe-centered whole-brain circuit and identify its putative neurophysiological impairments in mouse models of PTSD. Experience with behavioral studies, stereotactic surgeries, programming, whole-brain microscopy or causal neuroscience is a plus, but is not required. The successful candidate should be highly motivated and have the ability to successfully lead a research project. The Silva lab is affiliated to the Institute of Neuroscience at the National Research Council of Italy and is located at the Neurocenter of the Humanitas Research Hospital in Rozzano, MI (https://www.humanitas-research.org/). Applicants should contact Bianca Silva (bianca.silva@in.cnr.it) with a current CV and a motivation letter. The position is full-time for 1 year, and renewable for other two. The position is immediately available and is funded by a 3-year grant by Cariplo Foundation. Within the first year, application to prestigious international postdoctoral fellowships (EMBO, Marie Curie, HFSP) is highly encouraged. Selected candidates will be directly contacted for interviews. After interview two reference letters will be requested.

This webinar will showcase new approaches for electrophysiological recordings using our silicon neural probes and surface arrays combined with diverse optical methods such as wide-field or 2-photon imaging, fiber photometry, and optogenetic perturbations in awake, behaving mice. Multi-modal recording of single units and local field potentials across cortex, hippocampus and thalamus alongside calcium activity via GCaMP6F in cortical neurons in triple-transgenic animals or in hippocampal astrocytes via viral transduction are brought to bear to reveal hitherto inaccessible and under-appreciated aspects of coordinated dynamics in the brain.

The circadian release of endogenous glucocorticoids is essential in preparing and synchronizing the body’s daily physiological needs. Disruption in the rhythmic activity of glucocorticoids has been observed in individuals with a variety of cancer types, and blunting of this rhythm has been shown to predict cancer mortality and declines in quality of life. This suggests that a disrupted glucocorticoid rhythm is potentially a shared phenotype across cancers. However, where this phenomenon is driven by the cancer itself, and the causal mechanisms that link glucocorticoid rhythm dysfunction and cancer outcomes remain preliminary at best. The regulation of daily glucocorticoid activity has been well-characterized and is maintained, in part, by the coordinated response of the hypothalamic-pituitary-adrenal (HPA) axis, consisting of the suprachiasmatic nucleus (SCN) and corticotropin-releasing hormone-expressing neurons of the paraventricular nucleus of the hypothalamus (PVNCRH). Consequently, we set out to examine if cancer-induced glucocorticoid dysfunction is regulated by disruptions within these hypothalamic nuclei. In comparison to their tumor-free baseline, mammary tumor-bearing mice exhibited a blunting of glucocorticoid rhythms across multiple timepoints throughout the day, as measured by the overall levels and the slope of fecal corticosterone rhythms, during tumor progression. We further examined how peripheral tumors shape hypothalamic activity within the brain. Serial two-photon tomography for whole-brain cFos imaging suggests a disrupted activation of the PVN in mice with tumors. Additionally, we found GFP labeled CRH+ neurons within the PVN after injection of pseudorabies virus expressing GFP into the tumor, pointing to the PVN as a primary target disrupted by mammary tumors. Preliminary in vivo fiber photometry data show that PVNCRH neurons exhibit enhanced calcium activity during tumor progression, as compared to baseline (no tumor) activity. Taken together, this suggests that there may be an overactive HPA response during tumor progression, which in turn, may result in a subsequent negative feedback on glucocorticoid rhythms. Current studies are examining whether tumor progression modulates SCN calcium activity, how the transcriptional profile of PVNCRH neurons is changed, and test if manipulation of the neurocircuitry surrounding glucocorticoid rhythmicity alters tumor characteristics.

Nearly all motivated behaviors require the ability to associate outcomes with specific actions and make adaptive decisions about future behavior. The nucleus accumbens (NAc) is integrally involved in these processes. The NAc is a heterogeneous population primarily composed of D1 and D2 medium spiny projection (MSN) neurons that are thought to have opposed roles in behavior, with D1 MSNs promoting reward and D2 MSNs promoting aversion. Here we examined what types of information are encoded by the D1 and D2 MSNs using optogenetics, fiber photometry, and cellular resolution calcium imaging. First, we showed that mice responded for optical self-stimulation of both cell types, suggesting D2-MSN activation is not inherently aversive. Next, we recorded population and single cell activity patterns of D1 and D2 MSNs during reinforcement as well as Pavlovian learning paradigms that allow dissociation of stimulus value, outcome, cue learning, and action. We demonstrated that D1 MSNs respond to the presence and intensity of unconditioned stimuli – regardless of value. Conversely, D2 MSNs responded to the prediction of these outcomes during specific cues. Overall, these results provide foundational evidence for the discrete aspects of information that are encoded within the NAc D1 and D2 MSN populations. These results will significantly enhance our understanding of the involvement of the NAc MSNs in learning and memory as well as how these neurons contribute to the development and maintenance of substance use disorders.

Fiber photometry (FP) is an adaptable method for recording in vivo neural activity in freely behaving animals. It has become a popular tool in neuroscience due to its ease of use, low cost, the ability to combine FP with freely moving behavior, among other advantages. However, analysis of FP data can be a challenge for new users, especially those with a limited programming background. Here, we present Guided Photometry Analysis in Python (GuPPy), a free and open-source FP analysis tool. GuPPy is provided as a Jupyter notebook, a well-commented interactive development environment (IDE) designed to operate across platforms. GuPPy presents the user with a set of graphic user interfaces (GUIs) to load data and provide input parameters. Graphs produced by GuPPy can be exported into various image formats for integration into scientific figures. As an open-source tool, GuPPy can be modified by users with knowledge of Python to fit their specific needs.

Motivational drives are internal states that can be different even in similar interactions with external stimuli. Curiosity as the motivational drive for novelty-seeking and investigating the surrounding environment is for survival as essential and intrinsic as hunger. Curiosity, hunger, and appetitive aggression drive three different goal-directed behaviors—novelty seeking, food eating, and hunting— but these behaviors are composed of similar actions in animals. This similarity of actions has made it challenging to study novelty seeking and distinguish it from eating and hunting in nonarticulating animals. The brain mechanisms underlying this basic survival drive, curiosity, and novelty-seeking behavior have remained unclear. In spite of having well-developed techniques to study mouse brain circuits, there are many controversial and different results in the field of motivational behavior. This has left the functions of motivational brain regions such as the zona incerta (ZI) still uncertain. Not having a transparent, nonreinforced, and easily replicable paradigm is one of the main causes of this uncertainty. Therefore, we chose a simple solution to conduct our research: giving the mouse freedom to choose what it wants—double freeaccess choice. By examining mice in an experimental battery of object free-access double-choice (FADC) and social interaction tests—using optogenetics, chemogenetics, calcium fiber photometry, multichannel recording electrophysiology, and multicolor mRNA in situ hybridization—we uncovered a cell type–specific cortico-subcortical brain circuit of the curiosity and novelty-seeking behavior. We found in mice that inhibitory neurons in the medial ZI (ZIm) are essential for the decision to investigate an object or a conspecific. These neurons receive excitatory input from the prelimbic cortex to signal the initiation of exploration. This signal is modulated in the ZIm by the level of investigatory motivation. Increased activity in the ZIm instigates deep investigative action by inhibiting the periaqueductal gray region. A subpopulation of inhibitory ZIm neurons expressing tachykinin 1 (TAC1) modulates the investigatory behavior.