Dr. Chinnakkaruppan Adaikkan


Assistant Professor

Chinna received his Ph.D. degree in neurobiology in 2016 from the University of Haifa, Israel. He carried out his Ph.D. thesis research at the University of Haifa and at the RIKEN Center for Brain Science, Japan. He uncovered the principles of associative taste aversion learning and memory. He further pursued his postdoctoral research at the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology, USA (2016-2020), where he continued to work as a research scientist (2021-2022). He demonstrated the neural circuit basis of cognitive dysfunctions in mouse models of Alzheimer’s disease and how brain stimulation could modify Alzheimer’s pathophysiology and learning & memory. In the early summer of 2022, he joined as a faculty member in the Centre for Brain Research at the Indian Institute of Science.

 

The research in our laboratory aims to understand the neural mechanisms underlying cognitive and systemic defects in neurodegenerative diseases such as Alzheimer’s disease (AD). The overarching goal is to discover how AD-associated pathology affects external sensory representations, memory, and internal body state. In addition, we are leveraging our basic research program to applications relevant to human neurological diseases. In particular, we aim to understand the neurophysiological and molecular mechanisms of brain responses to brain stimulation. To investigate these areas of interest, we use a multidisciplinary approach utilizing various state-of-the-art techniques – including genetics in mice, viral manipulations, circuit tracing, optogenetics, high-density linear probe electrophysiology, in vivo imaging, and biochemical analysis. We focus on three broad questions:

  1. How do major neuronal cell types such as PV, SST, CaMKII, and CH neurons participate in transcranial electrical stimulation (tES) evoked responses?
  2. What are the neurophysiological and circuit principles of cognitive dysfunction and interoceptive integration in AD? We focus on the multisensory insular & prefrontal cortical (PFC) circuits.
  3. What are the brain and systemic responses to chronic tES in Alzheimer’s disease?

Mechanisms of Noninvasive Brain stimulations

We believe noninvasive brain stimulation such as transcranial electrical stimulation (tES) can have tremendous implications for neuro-engineering applications and the treatment of Alzheimer’s Disease, but only if we understand and precisely control the mechanisms of tES. While there is an extensive effort to evaluate the potential of tES to modify disease outcomes, we lack a comprehensive understanding of how they elicit their myriad effects. To fill this gap in knowledge,  we are currently investigating how different cell types, beautifully organized across the cortical layers, respond electrophysiologically and transcriptionally to tES. We test several tES paradigms such as anodal and cathodal tDCS (transcranial direct current stimulation) and theta & gamma tACS (transcranial alternating current stimulation). We focus on CaMKII excitatory neurons and PV and SST interneurons to study how these cell types regulate tES evoked electrical activity across the cortical layers locally. In addition, we have elucidated the indispensability of CH neurons in synchronizing neural activity between cerebral brain hemispheres. Therefore, we study if and how tES applied to one brain hemisphere affects the electrical activity in the contralateral brain hemisphere.

Neural Correlates of Memory and Systemic Defects in Alzheimer’s Disease

In the early stages of AD, the insular and prefrontal cortices exhibit a significant pathological burden, which coincides with glial activation. However, we still do not understand how the pathological burden in insular-prefrontal cortices affects cognitive and daily life activities in AD. For example, does AD-associated pathology in these brain areas lead to gain or loss of communication, under baseline and during cognitive tasks? What are the anatomical architecture and molecular and neurophysiological signatures? How do these brain areas regulate interoception as the insular and prefrontal cortices are implicated in various regulatory mechanisms, including drive and autonomic control? We acquire large multimodal datasets as control, and AD mouse models sleep or perform cognitive tasks. We perform deep learning to gain insights into the relationships between neural (local field potential and spikes), systemic signals (breath and heart rhythms), and cognitive performance. We use APP (amyloid precursor protein) knock-in mice containing a humanized APP gene with three AD-associated mutations as an AD mouse model.

Neural and Systemic Responses to Chronic tES in Alzheimer’s disease

Our goals are to discover how repeated tES application over the insular & prefrontal cortices influences mental and physical health in AD. We address these questions by leveraging viral and optogenetics tools to manipulate neural activity, tES, record the neural and systemic activity, and examine gene expression programs in major cell types. We believe that understanding the molecular, cellular, neural circuitry, and systemic underpinnings of repeated tES in AD will eventually uncover effective treatments.

Lab News

  1. Chinna has been recommended for DBT/Wellcome Trust India Alliance Intermediate Fellowships

Harsha Bhardwaj
PhD student

 

 

 

Dipanwita Santra
PhD student

 

 

  1. Chinnakkaruppan Adaikkan*, Jun Wang, Karim Abdelaal, Steven J. Middleton, P. Lorenzo Bozzelli, Ian R. Wickersham, Thomas J. McHugh, Li-Huei Tsai,
    Alterations in a cross-hemispheric circuit associates with novelty discrimination deficits in mouse models of neurodegeneration,
    Neuron, 2022,ISSN 0896-6273,https://doi.org/10.1016/j.neuron.2022.07.023.
  2. Marco A, Meharena HS, Dileep V, Raju RM, Davila-Velderrain J, Zhang AL, Adaikkan C, Young JZ, Gao F, Kellis M, Tsai LH. (2020) Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble. Nature Neuroscience. 23,1606–1617. https//doi.org/10.1038/s41593-020-00717-0
  3. Pao PC, Patnaik D, Watson LA, Gao F, Pan L, Wang J, Adaikkan C, Penney J, Cam HP, Huang WC, Pantano L, Lee A, Nott A, Phan TX, Gjoneska E, Elmsaouri S, Haggarty SJ, Tsai LH. (2020) HDAC1 modulates OGG1-initiated oxidative DNA damage repair, brain aging, and Alzheimer’s disease pathology. Nature communication. 11:2484. https://doi.org/10.1038/s41467-020-16361-y
  4. Adaikkan C and Tsai LH. (2020) Gamma Entrainment: Impact on Neurocircuits, Glia and Therapeutic Opportunities. Trends in Neurosciences. 43(1):24-41. https://doi.org/10.1016/j.tins.2019.11.001. This review article has been featured in Cell Press’s special collection on light! https://www.cell.com/trends/collections/light
  5. Adaikkan C, Middleton SJ, Marco A, Pao PC, Mathys H, Kim DNW, Gao F, Young JZ, Suk HJ, Boyden ES, McHugh TJ and Tsai LH. (2019) Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection. Neuron. 102(5): 929-943.e8. https://doi.org/10.1016/j.neuron.2019.04.011 Featured article in Neuron with previews. The paper has been covered in ‘Bench to Bedside in the Journal of the American Medical Association (JAMA)’ and ‘Editor’s choice in Science Translational Medicine’.
  6. Adaikkan C#, Taha E#, Barrera I, David O and Rosenblum K. (2018) Calcium/Calmodulin-Dependent Protein Kinase II and Eukaryotic Elongation Factor 2 Kinase Pathways Mediate the Antidepressant Action of Ketamine. Biol Psychiatry. 84(1): 65-75. https://doi.org/10.1016/j.biopsych.2017.11.028 #These authors contributed equally. Article accompanied by commentary. The paper has been recommended in F1000Prime as being of special significance in its field.
  7. Singer A, Martorell A, Douglas JM, Abdurrob F, Attokaren M, Tipton J, Mathys H, Adaikkan C and Tsai LH. (2018) Non-invasive 40 Hz light flicker to reduce amyloid load and recruit microglia. Nature protocols. 13(8): 1850-1868. https://doi.org/10.1038/s41596-018-0021-x
  8. Mathys H, Adaikkan C, Gao F, Young JZ, Manet E, Hemberg M, De Jager PL, Ransohoff RM, Regev A and Tsai LH. (2017) Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution. Cell Reports. 21(2):366-380. https://doi.org/10.1016/j.celrep.2017.09.039
  9. Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter RG, Rueda R, Brown EN, Boyden ES and Tsai LH. (2016) Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 540(7632):230-235. https://doi.org/10.1038/nature20587
  10. Miyamoto D, Hirai D, Fung CC, Inutsuka A, Odagawa M, Suzuki T, Boehringer R, Adaikkan C, Matsubara C, Matsuki N, Fukai T, McHugh TJ, Yamanaka A and Murayama M. (2016) Top-down cortical input during NREM sleep consolidates perceptual memory. Science. 352(6291):1315-8. 10.1126/science.aaf0902
  11. Adaikkan C and Rosenblum K. (2015) A molecular mechanism underlying gustatory memory trace for an association in the insular cortex. 21(2):37-51. https://doi.org/10.7554/eLife.07582.001
  12. C Adaikkan, Wintzer ME, McHugh TJ and Rosenblum K. (2014) Differential Contribution of Hippocampal Subfields to Components of Associative Taste Learning. Journal of Neuroscience. 34(33):11007-15. https://doi.org/10.1523/JNEUROSCI.0956-14.2014
  13. David O, Barrera I, C Adaikkan, Kaphzan H, Nakazawa T, Yamamoto T and Rosenblum K. (2014) Dopamine-induced tyrosine phosphorylation of NR2B (Tyr1472) is essential for ERK1/2 activation and processing of novel taste information. Front Mol Neurosci. 7:66. https://doi.org/10.3389/fnmol.2014.00066
  14. Stern E#, C Adaikkan#, David O, Sonenberg N and Rosenblum K. (2013) Blocking the eIF2? Kinase (PKR) Enhances Positive and Negative forms of Cortex-Dependent Taste Memory. Journal of Neuroscience. 33(6):2517-25. https://doi.org/10.1523/JNEUROSCI.2322-12.2013 #These authors contributed equally.
  15. Adaikkan C and Rosenblum K. (2012) The role of Protein Phosphorylation in the Gustatory Cortex and Amygdala During Taste Learning. Exp Neurobiol. 21(2):37-51. 10.5607/en.2012.21.2.37
  16. Isai M, Elanchezhian R, Sakthivel M, C Adaikkan, Rajamohan M, Jesudasan Nelson, Thomas PA and Geraldine P. (2009) Anticataractogenic Effect of an Extract of the Oyster Mushroom, Pleurotus ostreatus, in an Experimental Animal Model. Curr Eye Res. 34:4, 264-273. https://doi.org/10.1080/02713680902774069
  17. C Adaikkan, Das S and Sarkar PK. (2009) Age related and hypothyroidism related changes on the stoichiometry of neurofilament subunits in the developing rat brain. Int J Dev Neurosci. 27; 257–261. https://doi.org/10.1016/j.ijdevneu.2008.12.007

We are looking for highly motivated technical and postdoctoral researchers. So, if you are passionate about neuroscience and neuro-engineering, motivated and curious, we encourage you to be part of our team. 

Postdocs: Prospective postdocs are encouraged to send an email with a CV, a brief research statement, and career goals & expectations. Candidates with independent funding are highly encouraged to apply.  

Currently, we have one open postdoctoral fellow position. The project’s primary focus is a mechanistic understanding of noninvasive brain stimulations in neurodegenerative diseases.  

  1. Job Title: Postdoctoral Fellow 

Job Duties 

  • Designs, directs and conducts specialized and advanced research experiments. 
  • Evaluates and analyzes data. 
  • Designs and executes logical follow-up experiments, executes them, analyzes and interprets the data, and demonstrates competency in troubleshooting.  

Essential Qualifications  

  • Ph.D in bioinformatics, computer science, electrical, and electronics will be considered. Candidates who expect to complete the Ph.D. soon may also apply. 
  • Computational skills such as Python, R, or MATLAB  
  • Strong communication and documentation skills.  
  • Should be highly independent, organized, focused and hardworking.  
  • Should be an enthusiastic team player.  

Desirable skills 

  • Experience and publications related to animal research 
  • High throughput sequencing and/or electrophysiology data analysis skill(s). 

Benefits 

  • The salary will be based on the qualifications and experience of the candidate. The contract duration will be 3 years, extendable up to 5 years depending on performance. 

Application procedure and deadline 

  • Interested candidates should send their CV and a 500-word research statement and expectations to chinna@iisc.ac.in (with ‘Application for Postdoctoral Fellow’ in the email subject line). Only shortlisted candidates will be contacted. 

Centre for Brain Research
Indian Institute of Science Campus
CV Raman Avenue
Bangalore 560012. India.

Email: chinna[at]iisc.ac.in
Telephone: Office +91 80 2293 3747