Prefrontal cortex

…the mechanistic gap for anterior prefrontal cortex function", which investigates the lateral anterior prefrontal cortex - involved in planning, multitasking, reasoning, memory-retrieval monitoring and decision-making - using fMRI, structural MRI and diffusion-weighted imaging on the 3 T and

Sleep is an active state critical for processing emotional memories encoded during waking in both humans and animals. There is a remarkable overlap between the brain structures and circuits active during sleep, particularly rapid eye-movement (REM) sleep, and the those encoding emotions. Accordingly, disruptions in sleep quality or quantity, including REM sleep, are often associated with, and precede the onset of, nearly all affective psychiatric and mood disorders. In this context, a major biomedical challenge is to better understand the underlying mechanisms of the relationship between (REM)

Complex brain functions are realized through the coordinated activity of populations of neurons. To manipulate brain function, it is crucial for brain stimulation techniques to achieve targeted control at the level of neural populations. Electrical microstimulation (uStim) has the potential to create targeted activity states because different combinations of stimulation parameters (e.g., location of the stimulated electrode(s), current amplitude, and frequency) produce diverse neural population activity states. However, its use for this purpose has been hindered by the challenge of identifying

…Mechanistically, it is known that the prefrontal cortex (PFC) is dysfunctional in this disorder and that there is a general excitatory/inhibitory (E/I) imbalance in the schizophrenia brain. However, whether schizophrenia executive dysfunction can be specifically attributed to prefrontal E/I imbalance is unknown. Here, through a series of experiments across schizophrenia-relevant mouse models, we show the

The prefrontal cortex (PFC) is critical for flexible decision-making, and dynamical motifs have been identified in PFC population activity that could support certain aspects of this process (e.g., context-dependent line attractors for sensory input integration). PFC is also known to encode a plethora of decision-relevant variables, including task progression, action, and value. It remains an open question whether there are dynamical motifs that track all these variables to inform decisions. Further, it is unclear how outcome feedback alters neural representations of these variables and impacts

Two striatal subregions, the Dorsolateral Striatum (DLS) and the Dorsomedial Striatum (DMS) are thought to implement habitual and flexible, goal-directed behavior respectively. The DMS has been shown to be involved in tasks such as gating of information into working memory and accumulating evidence before making a decision. How the DMS produces these behaviors is less understood than the DLS because, unlike habitual motor tasks used to study the DLS, tasks used to study the DMS require more management of internal mental states, an inherently unobservable process. In this work, we build a compu

…that the mediodorsal (MD) thalamus and prefrontal cortex (PFC) are a pair of critical partners to achieve cognitive control. e found that such multiplicative thalamocortical gating enables a local Hebbian-weight amplification for prefrontal synaptic plasticity and is the key to facilitate a low-rank structure in prefrontal comput

Animals compose low-level actions in the service of high-level goals. Prefrontal cortex is essential for this organization when the goals are externally imposed, as in tasks where reward contingencies switch over time. Here we asked if it plays a similar role during spontaneous exploratory behaviors in the mouse. Using a hierarchical model, we identify stable patterns of action selection that capture emergent ‘task-states’ like wall following, object investigation or social interaction. These states align with distinct epochs of activity in medial prefrontal cortex (mPFC) – a coincidence that

The sleeping brain is in a constant tradeoff between maintaining its quiescent state, thought to support homeostatic processes, and interrupting it to deal with external contingencies such as threat. While evidence suggests that sleep interruption is an associative contextual process, little is known about its underlying neural substrates. Here, inspired by evidence that sleep interruption in humans relies on associative and contextual components, we develop a paradigm in mice to identify its circuit mechanisms. By training mice on an active avoidance task variant, we discover that auditory co

The mammalian Prefrontal Cortex (PFC) has been suggested to modulate sensory information processing across multiple cortical regions via long-range axonal projections. These axonal projections arise from discrete PFC subregions with unique brain-wide connectivity and functional repertoires, which may provide the architecture for modular feedback intended to shape sensory processing. Here, we used axonal tracing, axonal and somatic 2-photon calcium imaging, and chemogenetic manipulations in mice to delineate how projections from the Anterior Cingulate Cortex (ACA) and ventrolateral Orbitofronta

…outline our recent work on how the prefrontal cortex can signal to the hypothalamus to regulate sleep preparatory behaviours and sleep itself, and how other brain regions, including the ventral tegmental area, respond to psychosocial stress to induce beneficial sleep. I will also outline our work on examin

The prefrontal cortex (PFC) plays an important role in working memory [1], however, the underlying neural processes remains elusive. Studies on the hippocampus revealed that place cell sequences encode goal-directed behavior in rats [2]. In this study, we report about the existence of sequential activation patterns in PFC and their correlation with behavior in a working memory task. Experiments were conducted with one-photon calcium imaging in Thy1-GCaMP6f mice during an olfaction-guided spatial memory task in a three-arm arena consisting of sampling, choice, and reward conditions. In order to

…lower and higher layers of the visual cortex, the frontal eye field, and the prefrontal cortex, showed

Exploring the origins of animal and human behavior within cortical circuits remains a puzzle awaiting resolution. It is established that when animals and humans compare two stimuli (d1 and d2) separated by a delay interval (Fig. 1a), their perception is influenced by a perceptual bias, characterized by a contraction in the perception of the first stimulus towards its distribution’s mean (highlighted in red in Fig. 1a). To shed light on this effect, recurrent neural networks (RNNs) of spiking neurons were trained, and their behavior and firing activity were examined in comparison to those obser

Cognitive flexibility plays a key role in ensuring an individual's survival. The prefrontal cortex and striatum are both essential to cognitive flexibility but competing theories debate which structure among these two leads the role in detecting and representing new circumstances for a change, giving largely opposing predictions on neural activities in the prefrontal cortex and striatum during flexible behavior. We trained head-restrained mice to perform an action-outcome based dynamic foraging task and simultaneously recorded single-neuron activities in the medial prefrontal cortex (mPFC)

The prefrontal cortex (PFC) is known to be involved in working memory, executive control, attention, and decision making. It integrates internal information and states with external information from the environment which results in timely and appropriate behavioral responses. It remains unknown how distinct excitatory cell types within PFC contribute to population activity and behavior. We investigate two major excitatory cell types within the PFC - extratelencephalic (ET) and intratelencephalic (IT) neurons. Anatomical analysis in transgenic mouse lines shows that ET neurons project to subcor

Experiencing stress during adolescence profoundly alters the neural systems that control goal-directed flexible behaviour. These changes are persistent and are thought to drive behavioural inflexibility in adults, a hallmark symptom of several mental illnesses, including addiction, depression, obsessive compulsive disorder and schizophrenia. The ventral hippocampus (vH) is heavily impacted by stress, however, its role in flexible behaviour remains unclear, partially due to its heterogeneity. Thus, the current study investigates how individual vH projection populations contribute to behavioural

…Here, we investigated prefrontal cortex (PFC) alterations and cerebellum-PFC connectivity in the IB2 KO mouse model of ASD. Significant alterations in signal processing and plasticity have been reported in the cerebellar granular layer of IB2 KO mice, confirming the crucial cerebellar involvement in ASD pathophysiology. Given the PFC renowned role in ASD and its functional connections with the cerebellum, we explored the prelimbic cortex (PrL) microcircuitry in IB2 KO and WT mice at differe

Our ability to develop, learn, and adapt depends on the brain’s capacity to change over time. To analyze plasticity processes over time in individual animals, we introduced a novel technique that enables immediate-early gene (IEG) activity to be mapped noninvasively using magnetic resonance imaging (MRI). Using this method, called IEG BLUsH, we interrogated the spatiotemporal relationships between neural activity and plasticity gene induction in an opioid administration paradigm. IEG activity and functional MRI (fMRI) signals were recorded following fentanyl treatments lasting several days (Fi

The mouse prefrontal cortex (PFC) is an umbrella term for rostrally located neocortical brain regions. The anterior cingulate, pre- and infralimbic, orbital, agranular insular and secondary motor cortices are generally included in the PFC. The PFC is critically involved in the acquisition and expression of flexible behavioral responses to changing sensory information, and prefrontal signalling to (neocortical) sensory regions is assumed to be essential to these processes.In the present study, we characterized the anatomical organization of excitatory, prefrontal projections to neocortical sens

…junction, precuneus, and prefrontal cortex. The neural correlates reflecting on parent-child similarity have yet to be studied. Here, we describe task-based functional connectivi

Over recent years, there has been an increasing need for a better understanding of the identity and the roles of astrocytes and their involvement in cognitive abilities. Indeed, they play a crucial role in brain functions, they show primate-specific features, and they are relevant in several diseases. Investigations on astrocytes across evolution have rarely been performed. However, a comprehensive comparison of astrocytes in a diverse range of mammals is pivotal for understanding the morphology across species and the related modifications in gene expression and functions. Our project aims to

Astrocytes interact with neurons at a cellular and molecular level, modulating the synaptic formation, maturation, and function. Their unique morphology allows them to contact synaptic structures to sense, process, and respond to incoming signals. Astrocyte activation leads to intracellular calcium-dependent processes that ultimately modulate circuit function and animal behavior. The IP3 receptor type 2 knockout (IP3R2 KO) mouse model lacks calcium elevations upon astrocytic activation and, therefore, is a good model for studying the roles of intracellular calcium signaling in circuit function

…adjust levels of dopamine in the prefrontal cortex (PFC) through astroglial vesicular monoamine transporter 2 (aVMAT2). Our recent data also indicate aVMAT2 expression in the nucleus accumbens (NAcc)., As SUD engages common neural pathways involved in natural reward processing i