Biafra Ahanonu

All Publications

• Long-term optical imaging of the spinal cord in awake behaving mice. Nature methods Ahanonu, B., Crowther, A., Kania, A., Rosa-Casillas, M., Basbaum, A. I. 2024; 21 (12): 2363-2375

  Abstract

  Advances in optical imaging and fluorescent biosensors enable study of the spatiotemporal and long-term neural dynamics in the brain of awake animals. However, methodological difficulties and fibrosis limit similar advances in the spinal cord. Here, to overcome these obstacles, we combined in vivo application of fluoropolymer membranes that inhibit fibrosis, a redesigned implantable spinal imaging chamber and improved motion correction methods that together permit imaging of the spinal cord in awake behaving mice, for months to over a year. We demonstrated a robust ability to monitor axons, identified a spinal cord somatotopic map, performed months-long imaging in freely moving mice, conducted Ca2+ imaging of neural dynamics in behaving mice responding to pain-provoking stimuli and observed persistent microglial changes after nerve injury. The ability to couple in vivo imaging and behavior at the spinal cord level will drive insights not previously possible at a key location for somatosensory transmission to the brain.

  View details for DOI 10.1038/s41592-024-02476-3

  View details for PubMedID 39533007

  View details for PubMedCentralID 4853475

• Recording Pain-Related Brain Activity in Behaving Animals Using Calcium Imaging and Miniature Microscopes Contemporary Approaches to the Study of Pain Ahanonu, B., Corder, G. Humana, New York, NY. 2022

  View details for DOI 10.1007/978-1-0716-2039-7_13

• An amygdalar neural ensemble that encodes the unpleasantness of pain. Science (New York, N.Y.) Corder, G., Ahanonu, B., Grewe, B. F., Wang, D., Schnitzer, M. J., Scherrer, G. 2019; 363 (6424): 276–81

  Abstract

  Pain is an unpleasant experience. How the brain's affective neural circuits attribute this aversive quality to nociceptive information remains unknown. By means of time-lapse in vivo calcium imaging and neural activity manipulation in freely behaving mice encountering noxious stimuli, we identified a distinct neural ensemble in the basolateral amygdala that encodes the negative affective valence of pain. Silencing this nociceptive ensemble alleviated pain affective-motivational behaviors without altering the detection of noxious stimuli, withdrawal reflexes, anxiety, or reward. Following peripheral nerve injury, innocuous stimuli activated this nociceptive ensemble to drive dysfunctional perceptual changes associated with neuropathic pain, including pain aversion to light touch (allodynia). These results identify the amygdalar representations of noxious stimuli that are functionally required for the negative affective qualities of acute and chronic pain perception.

  View details for PubMedID 30655440

• Fiber photometry in striatum reflects primarily nonsomatic changes in calcium. Nature neuroscience Legaria, A. A., Matikainen-Ankney, B. A., Yang, B., Ahanonu, B., Licholai, J. A., Parker, J. G., Kravitz, A. V. 2022; 25 (9): 1124-1128

  Abstract

  Fiber photometry enables recording of population neuronal calcium dynamics in awake mice. While the popularity of fiber photometry has grown in recent years, it remains unclear whether photometry reflects changes in action potential firing (that is, 'spiking') or other changes in neuronal calcium. In microscope-based calcium imaging, optical and analytical approaches can help differentiate somatic from neuropil calcium. However, these approaches cannot be readily applied to fiber photometry. As such, it remains unclear whether the fiber photometry signal reflects changes in somatic calcium, changes in nonsomatic calcium or a combination of the two. Here, using simultaneous in vivo extracellular electrophysiology and fiber photometry, along with in vivo endoscopic one-photon and two-photon calcium imaging, we determined that the striatal fiber photometry does not reflect spiking-related changes in calcium and instead primarily reflects nonsomatic changes in calcium.

  View details for DOI 10.1038/s41593-022-01152-z

  View details for PubMedID 36042311

  View details for PubMedCentralID PMC10152879

• Supramammillary regulation of locomotion and hippocampal activity. Science (New York, N.Y.) Farrell, J. S., Lovett-Barron, M., Klein, P. M., Sparks, F. T., Gschwind, T., Ortiz, A. L., Ahanonu, B., Bradbury, S., Terada, S., Oijala, M., Hwaun, E., Dudok, B., Szabo, G., Schnitzer, M. J., Deisseroth, K., Losonczy, A., Soltesz, I. 2021; 374 (6574): 1492-1496

  Abstract

  [Figure: see text].

  View details for DOI 10.1126/science.abh4272

  View details for PubMedID 34914519

• Visually Guided Behavior and Optogenetically Induced Learning in Head-Fixed Flies Exploring a Virtual Landscape CURRENT BIOLOGY Haberkern, H., Basnak, M. A., Ahanonu, B., Schauder, D., Cohen, J. D., Bolstad, M., Bruns, C., Jayaraman, V. 2019; 29 (10): 1647-+

  Abstract

  Studying the intertwined roles of sensation, experience, and directed action in navigation has been facilitated by the development of virtual reality (VR) environments for head-fixed animals, allowing for quantitative measurements of behavior in well-controlled conditions. VR has long featured in studies of Drosophila melanogaster, but these experiments have typically allowed the fly to change only its heading in a visual scene and not its position. Here we explore how flies move in two dimensions (2D) using a visual VR environment that more closely captures an animal's experience during free behavior. We show that flies' 2D interaction with landmarks cannot be automatically derived from their orienting behavior under simpler one-dimensional (1D) conditions. Using novel paradigms, we then demonstrate that flies in 2D VR adapt their behavior in response to optogenetically delivered appetitive and aversive stimuli. Much like free-walking flies after encounters with food, head-fixed flies exploring a 2D VR respond to optogenetic activation of sugar-sensing neurons by initiating a local search, which appears not to rely on visual landmarks. Visual landmarks can, however, help flies to avoid areas in VR where they experience an aversive, optogenetically generated heat stimulus. By coupling aversive virtual heat to the flies' presence near visual landmarks of specific shapes, we elicit selective learned avoidance of those landmarks. Thus, we demonstrate that head-fixed flies adaptively navigate in 2D virtual environments, but their reliance on visual landmarks is context dependent. These behavioral paradigms set the stage for interrogation of the fly brain circuitry underlying flexible navigation in complex multisensory environments.

  View details for DOI 10.1016/j.cub.2019.04.033

  View details for Web of Science ID 000468409100024

  View details for PubMedID 31056392

• Kilohertz two-photon brain imaging in awake mice. Nature methods Zhang, T. n., Hernandez, O. n., Chrapkiewicz, R. n., Shai, A. n., Wagner, M. J., Zhang, Y. n., Wu, C. H., Li, J. Z., Inoue, M. n., Gong, Y. n., Ahanonu, B. n., Zeng, H. n., Bito, H. n., Schnitzer, M. J. 2019

  Abstract

  Two-photon microscopy is a mainstay technique for imaging in scattering media and normally provides frame-acquisition rates of ~10-30 Hz. To track high-speed phenomena, we created a two-photon microscope with 400 illumination beams that collectively sample 95,000-211,000 µm2 areas at rates up to 1 kHz. Using this microscope, we visualized microcirculatory flow, fast venous constrictions and neuronal Ca2+ spiking with millisecond-scale timing resolution in the brains of awake mice.

  View details for DOI 10.1038/s41592-019-0597-2

  View details for PubMedID 31659327

• Diametric neural ensemble dynamics in parkinsonian and dyskinetic states. Nature Parker, J. G., Marshall, J. D., Ahanonu, B. n., Wu, Y. W., Kim, T. H., Grewe, B. F., Zhang, Y. n., Li, J. Z., Ding, J. B., Ehlers, M. D., Schnitzer, M. J. 2018

  Abstract

  Loss of dopamine in Parkinson's disease is hypothesized to impede movement by inducing hypo- and hyperactivity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively. The opposite imbalance might underlie hyperkinetic abnormalities, such as dyskinesia caused by treatment of Parkinson's disease with the dopamine precursor L-DOPA. Here we monitored thousands of SPNs in behaving mice, before and after dopamine depletion and during L-DOPA-induced dyskinesia. Normally, intermingled clusters of dSPNs and iSPNs coactivated before movement. Dopamine depletion unbalanced SPN activity rates and disrupted the movement-encoding iSPN clusters. Matching their clinical efficacy, L-DOPA or agonism of the D2 dopamine receptor reversed these abnormalities more effectively than agonism of the D1 dopamine receptor. The opposite pathophysiology arose in L-DOPA-induced dyskinesia, during which iSPNs showed hypoactivity and dSPNs showed unclustered hyperactivity. Therefore, both the spatiotemporal profiles and rates of SPN activity appear crucial to striatal function, and next-generation treatments for basal ganglia disorders should target both facets of striatal activity.

  View details for PubMedID 29720658

• Neuronal Representation of Social Information in the Medial Amygdala of Awake Behaving Mice CELL Li, Y., Mathis, A., Grewe, B. F., Osterhout, J. A., Ahanonu, B., Schnitzer, M. J., Murthy, V. N., Dulac, C. 2017; 171 (5): 1176-+

  Abstract

  The medial amygdala (MeA) plays a critical role in processing species- and sex-specific signals that trigger social and defensive behaviors. However, the principles by which this deep brain structure encodes social information is poorly understood. We used a miniature microscope to image the Ca2+ dynamics of large neural ensembles in awake behaving mice and tracked the responses of MeA neurons over several months. These recordings revealed spatially intermingled subsets of MeA neurons with distinct temporal dynamics. The encoding of social information in the MeA differed between males and females and relied on information from both individual cells and neuronal populations. By performing long-term Ca2+ imaging across different social contexts, we found that sexual experience triggers lasting and sex-specific changes in MeA activity, which, in males, involve signaling by oxytocin. These findings reveal basic principles underlying the brain's representation of social information and its modulation by intrinsic and extrinsic factors.

  View details for PubMedID 29107332

  View details for PubMedCentralID PMC5731476

• SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons NATURE NEUROSCIENCE Dobbin, M. M., Madabhushi, R., Pan, L., Chen, Y., Kim, D., Gao, J., Ahanonu, B., Pao, P., Qiu, Y., Zhao, Y., Tsai, L. 2013; 16 (8): 1008-U54

  Abstract

  Defects in DNA repair have been linked to cognitive decline with age and neurodegenerative disease, yet the mechanisms that protect neurons from genotoxic stress remain largely obscure. We sought to characterize the roles of the NAD(+)-dependent deacetylase SIRT1 in the neuronal response to DNA double-strand breaks (DSBs). We found that SIRT1 was rapidly recruited to DSBs in postmitotic neurons, where it showed a synergistic relationship with ataxia telangiectasia mutated (ATM). SIRT1 recruitment to breaks was ATM dependent; however, SIRT1 also stimulated ATM autophosphorylation and activity and stabilized ATM at DSB sites. After DSB induction, SIRT1 also bound the neuroprotective class I histone deacetylase HDAC1. We found that SIRT1 deacetylated HDAC1 and stimulated its enzymatic activity, which was necessary for DSB repair through the nonhomologous end-joining pathway. HDAC1 mutations that mimic a constitutively acetylated state rendered neurons more susceptible to DNA damage, whereas pharmacological SIRT1 activators that promoted HDAC1 deacetylation also reduced DNA damage in two mouse models of neurodegeneration. We propose that SIRT1 is an apical transducer of the DSB response and that SIRT1 activation offers an important therapeutic avenue in neurodegeneration.

  View details for DOI 10.1038/nn.3460

  View details for Web of Science ID 000322323000010

  View details for PubMedID 23852118

  View details for PubMedCentralID PMC4758134

• On the Technology Prospects and Investment Opportunities for Scalable Neuroscience arXiv Dean, T., Ahanonu, B., et al 2013; 1307 (7302)