Adaptation to photoperiod via dynamic neurotransmitter segregation.

Changes in the amount of daylight (photoperiod) alter physiology and behaviour1,2. Adaptive responses to seasonal photoperiods are vital to all organisms-dysregulation associates with disease, including affective disorders3 and metabolic syndromes4. The circadian rhythm circuitry is implicated in such responses5,6, yet little is known about the precise cellular substrates that underlie phase synchronization to photoperiod change. Here we identify a brain circuit and system of axon branch-specific and reversible neurotransmitter deployment that are critical for behavioural and sleep adaptation to photoperiod. A type of neuron called mrEn1-Pet17 in the mouse brainstem median raphe nucleus segregates serotonin from VGLUT3 (also known as SLC17A8, a proxy for glutamate) to different axonal branches that innervate specific brain regions involved in circadian rhythm and sleep-wake timing8,9. This branch-specific neurotransmitter deployment did not distinguish between daylight and dark phase; however, it reorganized with change in photoperiod. Axonal boutons, but not cell soma, changed neurochemical phenotype upon a shift away from equinox light/dark conditions, and these changes were reversed upon return to equinox conditions. When we genetically disabled Vglut3 in mrEn1-Pet1 neurons, sleep-wake periods, voluntary activity and clock gene expression did not synchronize to the new photoperiod or were delayed. Combining intersectional rabies virus tracing and projection-specific neuronal silencing, we delineated a preoptic area-to-mrEn1Pet1 connection that was responsible for decoding the photoperiodic inputs, driving the neurotransmitter reorganization and promoting behavioural synchronization. Our results reveal a brain circuit and periodic, branch-specific neurotransmitter deployment that regulates organismal adaptation to photoperiod change.

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.

[Asthma in pregnancy. Physiopathological, clinical, and therapeutic aspects]. / Asma in gravidanza. Aspetti fisiopatologici, clinici e terapeutici.

The constantly increasing frequency of asthmatic pathologies in the general population has consequently led to a greater number of cases of bronchial asthma in pregnant women. In normal conditions the respiratory function undergoes numerous modifications in pregnancy, above all increased ventilation/minute and oxygen consumption. Likewise, asthma has a number of obviously negative effects both on the pregnant woman and the developing foetus. The clinical course of asthma may also be influenced by the start of pregnancy in various unforeseeable ways. All these aspects highlight the considerable difficulties of treating bronchial asthma during pregnancy, not to mention the medicolegal responsibility which the obstetrician and doctor must assume. In this respect it is vitally important to emphasize that pregnant women suffering from asthma must be treated in the same way as those who are not pregnant, and both prophylactic and anti-dysreactive pharmacological treatment must be administered at an early stage right up until the time of birth. Since these drugs are above all of the aerosol type, their potential secondary and/or teratogenic effects is considered extremely low and to all extents absolutely favourable in relation to the cost/benefit ratio. In fact, it is certainly less damaging for the pregnant woman to take these drugs, even in the first trimester of pregnancy, rather than run the risk of an attack of asthma with unforeseeable results. It is therefore enormously important to ensure that both the doctor and pregnant woman are adequately informed regarding preventive and pharmacological strategies for bronchial asthma.