TY - JOUR
T1 - Sensorimotor coding of vermal granule neurons in the developing mammalian cerebellum
AU - Markwalter, Kelly H.
AU - Yang, Yue
AU - Holy, Timothy E.
AU - Bonni, Azad
N1 - Funding Information:
Received Jan. 11, 2019; revised May 18, 2019; accepted June 18, 2019. Author contributions: K.H.M., T.E.H., and A.B. designed research; K.H.M. performed research; K.H.M., Y.Y., and T.E.H.analyzeddata;K.H.M.wrotethefirstdraftofthepaper;Y.Y.editedthepaper;T.E.H.andA.B.wrotethepaper. This work was supported by National Institutes of Health Grant NS041021 to A.B. and Grant NS068409 to T.E.H., the Mathers Foundation to A.B., and National Institutes of Health Medical Scientist Training Program Grant T32 GM07200toK.H.M.WethankthemachineshopatWashingtonUniversityandtheWashingtonUniversityCenterfor CellularImagingfortechnicalsupport;andMarthaBagnall,PabloBlazquez,EdHan,andmembersoftheBonniand Holy laboratories for helpful discussions and critical review of the manuscript. The authors declare no competing financial interests. Correspondence should be addressed to Azad Bonni at bonni@wustl.edu or Timothy E. Holy at holy@wustl.edu. Y. Yang’s present address: Department of Neurobiology, Northwestern University, Evanston, IL 60208. https://doi.org/10.1523/JNEUROSCI.0086-19.2019 Copyright © 2019 the authors
Publisher Copyright:
© 2019 the authors.
PY - 2019/8/21
Y1 - 2019/8/21
N2 - The vermal cerebellum is a hub of sensorimotor integration critical for postural control and locomotion, but the nature and developmental organization of afferent information to this region have remained poorly understood in vivo. Here, we use in vivo two-photon calcium imaging of the vermal cerebellum in awake behaving male and female mice to record granule neuron responses to diverse sensorimotor cues targeting visual, auditory, somatosensory, and motor domains. Use of an activity-independent marker revealed that approximately half (54%) of vermal granule neurons were activated during these recordings. A multikernel linear model distinguished the relative influences of external stimuli and co-occurring movements on neural responses, indicating that, among the subset of activated granule neurons, locomotion (44%-56%) and facial air puffs (50%) were more commonly and reliably encoded than visual (31%-32%) and auditory (19%-28%) stimuli. Strikingly, we also uncover populations of granule neurons that respond differentially to voluntary and forced locomotion, whereas other granule neurons in the same region respond similarly to locomotion in both conditions. Finally, by combining two-photon calcium imaging with birth date labeling of granule neurons via in vivo electroporation, we find that early- and late-born granule neurons convey similarly diverse sensorimotor information to spatially distinct regions of the molecular layer. Collectively, our findings elucidate the nature and developmental organization of sensorimotor information in vermal granule neurons of the developing mammalian brain.
AB - The vermal cerebellum is a hub of sensorimotor integration critical for postural control and locomotion, but the nature and developmental organization of afferent information to this region have remained poorly understood in vivo. Here, we use in vivo two-photon calcium imaging of the vermal cerebellum in awake behaving male and female mice to record granule neuron responses to diverse sensorimotor cues targeting visual, auditory, somatosensory, and motor domains. Use of an activity-independent marker revealed that approximately half (54%) of vermal granule neurons were activated during these recordings. A multikernel linear model distinguished the relative influences of external stimuli and co-occurring movements on neural responses, indicating that, among the subset of activated granule neurons, locomotion (44%-56%) and facial air puffs (50%) were more commonly and reliably encoded than visual (31%-32%) and auditory (19%-28%) stimuli. Strikingly, we also uncover populations of granule neurons that respond differentially to voluntary and forced locomotion, whereas other granule neurons in the same region respond similarly to locomotion in both conditions. Finally, by combining two-photon calcium imaging with birth date labeling of granule neurons via in vivo electroporation, we find that early- and late-born granule neurons convey similarly diverse sensorimotor information to spatially distinct regions of the molecular layer. Collectively, our findings elucidate the nature and developmental organization of sensorimotor information in vermal granule neurons of the developing mammalian brain.
KW - Calcium imaging
KW - Cerebellar development
KW - Cerebellar granule neuron
KW - Sensorimotor encoding
KW - Two-photon imaging
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U2 - 10.1523/JNEUROSCI.0086-19.2019
DO - 10.1523/JNEUROSCI.0086-19.2019
M3 - Article
C2 - 31235645
AN - SCOPUS:85071703399
SN - 0270-6474
VL - 39
SP - 6626
EP - 6643
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 34
ER -