Biology subjects

Maddaloni, G.

Publications and source records attributed to Maddaloni, G..

3 recordsLinked to original sources

bioRxiv2023

A brain circuit and neuronal mechanism for decoding and adapting to change in daylength

Changes in daylight amount (photoperiod) drive pronounced alterations in physiology and behaviour1,2. Adaptive responses to seasonal photoperiods are vital to all organisms - dysregulation is associated with disease, from affective disorders3 to metabolic syndromes4. Circadian rhythm circuitry has been implicated5,6 yet little is known about the precise neural and cellular substrates that underlie phase synchronization to photoperiod change. Here we present a previously unknown brain circuit and novel system of axon branch-specific and reversible neurotransmitter deployment that together prove critical for behavioural and sleep adaptation to photoperiod change. We found that the recently defined neuron type called mrEn1-Pet17 located in the mouse brainstem Median Raphe Nucleus (MRN) segregates serotonin versus VGLUT3 (here proxy for the neurotransmitter glutamate) to different axonal branches innervating specific brain regions involved in circadian rhythm and sleep/wake timing8,9. We found that whether measured during the light or dark phase of the day this branch-specific neurotransmitter deployment in mrEn1-Pet1 neurons was indistinguishable; however, it strikingly reorganizes on photoperiod change. Specifically, axonal boutons but not cell soma show a shift in neurochemical phenotype upon change away from equinox light/dark conditions that reverses upon return to equinox. When we genetically disabled the deployment of VGLUT3 in mrEn1-Pet1 neurons, we found that sleep/wake periods and voluntary activity failed to synchronize to the new photoperiod or was significantly delayed. Combining intersectional rabies virus tracing and projection-specific neuronal silencing in vivo, we delineated a Preoptic Area-to-mrEn1Pet1 connection responsible for decoding the photoperiodic inputs, driving the neurochemical shift and promoting behavioural synchronization. Our results reveal a previously unrecognized brain circuit along with a novel form of periodic, branch-specific neurotransmitter deployment that together regulate organismal adaptation to photoperiod changes.

neuroscience↗

bioRxiv2017

Brainwide Mapping Of Endogenous Serotonergic Transmission Via Chemogenetic-fMRI

Serotonergic transmission affects behaviours and neuro-physiological functions via the orchestrated recruitment of distributed neural systems. It is however unclear whether serotonins modulatory effect entails a global regulation of brainwide neural activity, or is relayed and encoded by a set of primary functional substrates. Here we combine DREADD-based chemogenetics and mouse fMRI, an approach we term \"chemo-fMRI\", to causally probe the brainwide substrates modulated by phasic serotonergic activity. We describe the generation of a conditional knock-in mouse line that, crossed with serotonin-specific Cre-recombinase mice, allowed us to remotely stimulate serotonergic neurons during fMRI scans. We show that chemogenetic stimulation of the serotonin system does not affect global brain activity, but results in region-specific activation of a set of primary target regions encompassing parieto-cortical, hippocampal, and midbrain structures, as well as ventro-striatal components of the mesolimbic reward systems. Many of the activated regions also exhibit increased c-Fos immunostaining upon chemogenetic stimulation in freely-behaving mice, corroborating a neural origin for the observed functional signals. These results identify a set of regional substrates that act as primary functional targets of endogenous serotonergic stimulation, and establish causation between phasic activation of serotonergic neurons and regional fMRI signals. They further highlight a functional cross-talk between serotonin and mesolimbic dopamine systems hence providing a novel framework for understanding serotonin dependent functions and interpreting data obtained from human fMRI studies of serotonin modulating agents.

neuroscience↗

bioRxiv2017

Serotonin Buffers Hippocampal Neuroplasticity And Emotional Behavior

Adaptation to environmental insults is an evolutionary mechanism essential for survival. The hippocampus participates in controlling adaptive responses to stress and emotional state through the modulation of neuroplasticity events, which are dysregulated in stress-related neuropsychiatric disorders. The neurotransmitter serotonin (5-HT) has been proposed as a pivotal player in hippocampal neuroplasticity in both normal and neuropsychiatric conditions though its role remains still poorly understood. Here, we investigated the impact of 5-HT deficiency on hippocampal activity combining RNA-seq, in vivo neuroimaging, neuroanatomical, biochemical and behavioral experiments on 5-HT depleted mice. We unveil that serotonin is required for appropriate activation of neuroplasticity adaptive mechanisms to environmental insults. Bidirectional deregulation of these programs in serotonin depleted mice is associated with opposite behavioral traits that model core symptoms of bipolar disorder. These findings delineate a previously unreported buffering role of 5-HT in instructing hippocampal activity and emotional responses to environmental demands.

neuroscience↗