Extended Flight Bouts Require Disinhibition from GABAergic Mushroom Body Neurons
authors: Steffy B. Manjila, Maria Kuruvilla, Jean-Francois Ferveur, Sanjay P. Sane, Gaiti Hasan
doi: 10.1016/j.cub.2018.11.070
CITATION
Manjila, S. B., Kuruvilla, M., Ferveur, J.-F., Sane, S. P., & Hasan, G. (2019). Extended Flight Bouts Require Disinhibition from GABAergic Mushroom Body Neurons. Current Biology, 29(2), 283-293.e5. https://doi.org/10.1016/j.cub.2018.11.070
ABSTRACT
fleeting notes
flight requires integration of muiltple sensory inputs and flight outputs
inhibition of octopaminergic and dopaminergic neurons OR activation of gabaergic MVONs reduce duration of flight
disinhibition of identified neural circuits occurs after flight initiation
- this is required to maintain flight state
path and duration of insect flight is deterined by sensory integration - and this happens in the central brain — but what about in the VNC?
MBs integrate internal state with external cues
PAM-DAN activity modulates synaptic outputs of MB lobes
- PAM-DAN activity may be modulated by OA
disruption of OA reduces flight duration
OA inputs from the SEZ activate PAM neurons which inhibits MBON-B1 to maintain longer flight bouts
used CaMPARI - irreversible conversion of green to red fluorescent protein when neural activity and UV light coincide
- used this to show that PAM-DAN neurons were active during tethered flight
knockdown of OA receptors reduces flight duration to a couple of minutes
knockdown in adults reduced flight but knockdown in early developmental stages did not effect flight
silencing PAM neurons also results in shorter flight
blocking OA synaptic release with Shibire reduced flight duration
OA-VPM4 neurons are required for maintenance of flight
- ventral paired medial 4 neurons
neural activity of PAM-MB B’1 modulates flight bout durations
octopamine activates PAM-DANs which inhibits MBON-B1 for maintenance of flight
octopamine sustains flight through an indirect disinhibition pathway
they did a ton of controls to show that Oamb is required in PAM-DANs for normal odor guided free flight
-
they ruled out flight initiation, ability to smell, motivation to feed
highlights
“Insect flight is a complex behavior that requires the integration of multiple sensory inputs with flight motor output.”Page 2
“Certain classes of dopaminergic and octopaminergic neurons that project to the mushroom body, a higher integrating center in the insect brain, are known to modify neuronal output based on contextual cues and thereby organismal behavior.”Page 2
“Either inhibition of octopaminergic and dopaminergic neurons or activation of GABAergic MBONs reduces the duration of flight bouts.”Page 2
“Our data suggest that disinhibition of the identified neural circuit very likely occurs after flight initiation and is required to maintain the ‘‘flight state’’ when searching for distant sites, possibly related to food sources, mating partners, or a suitable egg-laying site”Page 2
“The path and duration of insect flight is determined by the integration of multiple sensory inputs and their coordination with the flight motor circuit. Such integration occurs in discrete but connected centers of the insect central brain [”Page 2
“In addition to the CC, flight is also modulated by antennal mechanosensory neurons located in the AMMC (antennal mechanosensory and motor center), that receive inputs from Johnston’s organs and regulate wing motor reflexes during flight”Page 2
“The function of PAM-DANs has primarily been investigated in the context of olfactory learning and memory, where they send reward as well as aversive signals, based on appropriate olfactory cues to synapses in the mushroom bodies (MBs)—another higher brain cente”Page 2
“we show that octopaminergic inputs, including neurons from the sub-esophageal zone (SEZ), activate PAM b’1 neurons, which inhibit MBON-b’1 to maintain longer flight bouts.”Page 2
“Green to red fluorescence shifts were observed in a subset of PAM neurons from dissected brain samples, when UV exposure was coupled with air-puffstimulated flight”Page 3
“we tested flight bout durations after knockdown of octopaminergic receptors on PAM neurons. Significant deficits in flight bout durations were observed by knockdown of Oamb and Octb1 receptor with the PAM-DANs GAL4 strain”Page 3
“flight deficits were also observed in Oamb584, an Oambnull mutant”Page 3
“that were rescued to a modest extent by overexpressing a transgene encoding Oamb in PAM neurons”Page 3
“Flight bouts were reduced significantly upon Oamb knockdown in PAM neurons of adults ( 200 s) as compared to controls”Page 3
“xpression of Shits in adult octopaminergic neurons followed by a shift to the non-permissive temperature of 30 C significantly reduced flight bout durations in OA>Shits ( 250 s) as compared to controls ( 500 s”Page 3
“Inactivation of synaptic vesicle recycling in neurons marked by MB113C-GAL4 (marks VPM4 neurons exclusively, henceforth referred to as VPM4-GAL4) resulted in flight deficits comparable to those observed with other subset GAL4s, which mark neurons other than VPM4”Page 3
“he OA-VPM4 neurons are required for maintenance of longer flight bouts”Page 3
“Therefore, PAM neurons receive octopaminergic inputs from the VPM4 neurons, together with inputs from other as yet unidentified OA neurons.”Page 3
“significant reduction in flight was observed by Oamb knockdown in PAM neurons that project to MB-b’1”Page 4
“the flight bout deficits arise from PAM projections to the b’1 lobe.”Page 5
“aken together, these data suggest that neuronal activity in PAM-MB b’1, b’2, g modulates flight bout durations, but the requirement for Oamb, in the context of flight, is most likely specific to PAM-b’1”Page 5
“MBON-b’1 inhibition permits extended flight bouts”Page 6
“These data suggest that inhibition of the identified MBON-b’1 allows flight bout durations to the same extent as in controls.”Page 6
“uggesting that increasing GABA release from MBON-b’1 by their activation decreases the duration of flight bouts.”Page 7
“we hypothesized that long flight bouts require OA-stimulated activity in PAM-DANs that in turn inhibits GABAergic MBON-b’1”Page 7
“activation of PAM-DANs evoked by CsChrimson inhibits the activity of MBON-b’1. Taken together, these data support the idea that maintenance of flight bout durations requires OA-stimulated dopamine release for inhibition of activity in GABAergic outputs from MBONs of the b’1 lobe.”Page 7
“. Thus, Oamb is required in PAM-DANs for normal odor-guided free flight in semi-natural conditions and the absence of octopaminergic inputs to the PAM-DANs results in flies with reduced durations of flight bouts after normal flight initiatio”Page 9
“Our data support a circuit where octopaminergic inputs to PAMDANs reduce inhibitory GABAergic outputs of MBONs to central brain centers that process visual (FB), gustatory (SEZ), and other”Page 9
“Based on these data, we speculate that OA-VPM4 neurons in the SEZ receive a range of sensory information that includes availability of food sources and food intake, and together, such inputs to the OA-VPM4 interneurons help maintain the fly’s ‘‘flight state’’ by stimulation of the PAM-DANs”Page 10
“erhaps, in a fly’s natural environment, different classes of sensory stimuli are received by separate DANs, modulating the outputs of distinct MB lobes.”Page 10
“During rest, GABA released from the MBONs might inhibit neuronal inputs to downstream neurons, in this case, most likely neurons of the flight central pattern generator that control activity of the flight motoneurons, thus inhibiting flight. When flight needs to be maintained for a longer period, the appropriate sensory stimuli relieve this GABAergic inhibition, resulting in longer durations of flight.”Page 10