Physiology - Research Publications

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Author: Bassi, Jaspreet × Author: Huf, Angela × Author: Del Rosso De Melo, Mariana ×

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    A Chemogenetic Tool that Enables Functional Neural Circuit Analysis
    Ngo, HB ; Melo, MR ; Layfield, S ; Connelly, AA ; Bassi, JK ; Xie, L ; Menuet, C ; McDougall, SJ ; Bathgate, RAD ; Allen, AM (CELL PRESS, 2020-09-15)
    Chemogenetics enables manipulation of neuronal activity in experimental animals. While providing information about the transduced neuron expressing a ligand-activated molecule, chemogenetics does not provide understanding about the antecedent circuit that drives that neuron's activity. For current approaches, this is not feasible, because the activating molecules are not genetically encoded. The insect allatostatin/allatostatin receptor system, a highly specific, powerful inhibitory chemogenetic approach, has this advantage, because the ligand, being a peptide, is genetically encoded. We developed viral vector-based systems to express biologically active allatostatin in neurons in vivo and allatostatin receptors in subpopulations of postsynaptic neurons. We demonstrate that activity-dependent release of allatostatin induces inhibition of allatostatin receptor-expressing neurons. We validate the approach in the vagal viscerosensory system where inhibitory, rather than the usual excitatory, viscerosensory input leads to sustained decreases in baroreceptor reflex sensitivity and bodyweight.
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    PreBotzinger complex neurons drive respiratory modulation of blood pressure and heart rate
    Menuet, C ; Connelly, AA ; Bassi, JK ; Melo, MR ; Le, S ; Kamar, J ; Kumar, NN ; McDougall, SJ ; McMullan, S ; Allen, AM (ELIFE SCIENCES PUBLICATIONS LTD, 2020-06-15)
    Heart rate and blood pressure oscillate in phase with respiratory activity. A component of these oscillations is generated centrally, with respiratory neurons entraining the activity of pre-sympathetic and parasympathetic cardiovascular neurons. Using a combination of optogenetic inhibition and excitation in vivo and in situ in rats, as well as neuronal tracing, we demonstrate that preBötzinger Complex (preBötC) neurons, which form the kernel for inspiratory rhythm generation, directly modulate cardiovascular activity. Specifically, inhibitory preBötC neurons modulate cardiac parasympathetic neuron activity whilst excitatory preBötC neurons modulate sympathetic vasomotor neuron activity, generating heart rate and blood pressure oscillations in phase with respiration. Our data reveal yet more functions entrained to the activity of the preBötC, with a role in generating cardiorespiratory oscillations. The findings have implications for cardiovascular pathologies, such as hypertension and heart failure, where respiratory entrainment of heart rate is diminished and respiratory entrainment of blood pressure exaggerated.