Understanding brain circuits that control brains states and homeostasis
Research Projects
Understanding Brain homesotasis
Of neurons and astrocytes
The Gutierrez-Herrera lab has expertise in the investigation of circuitries that control sleep and sleep homeostasis in health and disease. Describing the cells that compose sleep-wake networks, their dynamics and how these are orchestrated across the brain have been my main research goal for the last few years. Her work of sleep circuit dissection includes the dissection of a novel sleep-wake circuit from the hypothalamus and thalamocortical networks, for which she was awarded the prestigious Pfizer Price in 2017. Since then, her contribution to the field of sleep research has continued with important findings, including other discoveries of sleep circuits – circuits for the eye movement during REM sleep as well as the function of sleep, including in vivo plasticity of hypothalamic GABAergic networks during sleep related to innate – food - behaviours using microendoscopy Ca2+ imaging in freely moving animal and the role of sleep spindles for the onset of rapid eye movement. In 2018 she started her own research group as part of the - Zentrum für experimentelle Neurologie- at the University of Bern, Switzerland. Currently, her projects are centred on the identification and functional characterizations of the neuron and astrocytes networks involved in sleep-dependant plasticity, sensory processing and cognition with a special emphasis in mental (part of the Interfaculty Research Cooperations (IRC) “Decoding Sleep: from neurons to health and Mind “) and psychiatric disorders (Schizophrenia and depression). Her group uses in vivo optogenetics, multisite in vivo electrophysiology and Ca2+ imaging in freely-moving mice, and recent behavioural phenotyping related to sleep-dependent memory consolidation, sensory processing, food behaviours, stress, anxiety and depression.
Brain circuits regulating brain states
Our team currently investigates the role of thalamocortical networks in brain state switching, sensory processing and consciousness. Interest was born from the novel description of GABAergic long-range connectivity between the lateral hypothalamus (LH) GABA cells. We have followed up with the role of the TRN GABAergic cells (TRNGABA)-Anterior dorsal thalamic (AD) projections in spindle generation and NREM regulation. We found that optogenetics stimulation of this circuit increased the spindle rate and promoted transitions to REM sleep. These novel findings highlighted the role of AD as a critical player in the thalamic circuit (TRNGABA-AD), modulating NREM stability and REM sleep transitions. Interestingly, in a separate project, the central medial thalamus is anatomically connected with the anterior cingulate (ACC), that in turn sends projections to the AD. We showed that neurons from the central medial thalamus exerted a dual arousal and sleep role depending on their firing mode, and CMT-ACC-AD allow the propagation of slow wave activity. The importance of these networks has been recently highlighted to be important in REM sleep-specific emotional processing. In trying to further understand the neural substrates of REM sleep features, together with my collaborators (Prof. M. Celio, University of Fribourg), we identified the brainstem circuit that controls eye movements during REM sleep.
Neurophysiology of psychiatric dissorders
Sleep disorders are common in psychiatric disorders and its thought that may share common neuronal underpinnings. Recently we found that a mouse model relevant to schizophrenia has challenged homeostatic responses. Interestingly depression and autism are also been suggested to have impaired synaptic homeostatic processes. Here we aim to investigate the underlying circuits that may be affected and could be modulated to treat brain homeostatic deficits.
Stroke
In this project, we investigate the role of specific brain circuits that may be in the cellular underlying sleep deficits and cognition present in patients. Further, we use optogenetics and auditory stimulation in trying to recover lost homeostatic responses, and sensory and cognitive
during recovery in freely moving mice. Thus far, we found medial thalamic, but not lateral thalamic lesions, resulting in sleep fragmentation and reduced frontal spindles with working memory alterations, similar to stroke patients, which may be due to changes in thalamocortical connectivity.
Our work aims to provide with novel insights into cortical and subcortical networks responsible for sleep-wake control and the potential identification of specific targets for sleep-related therapies common in neurological disorders such as stroke.
Tools
In the lab, we use cutting-edge technologies ranging from molecular genetics, in vivo electrophysiology and calcium imaging of single-cell and multiplex systems (from the cellular, molecular level) to behavioural phenotyping.
If you want to learn more about our research, please don’t hesitate to get in touch.