Centre for Brain Research, IISc


Smitha Karunakaran's Lab


Smitha Karunakaran

Smitha Karunakaran, PhD
Assistant Professor at the Centre for Brain Research

Research Interest: Circuit mechanisms underlying dementia including Alzheimer's Disease

Email: smitha[at]iisc.ac.in
Telephone: Office +91 80 2293 3639


The primary goal of our laboratory is to understand the circuit based mechanisms underlying dementia. Dementia encompasses many different conditions including Alzheimer's Disease (AD), Frontotemporal dementia, Vascular dementia among others. AD is one of the most common forms of dementia worldwide. It is an irreversible, progressive neurodegenerative disorder that slowly impairs memory and higher cognitive functions. Longitudinal studies in humans have revealed that accumulation of beta-amyloid, synaptic dysfunction observed as decreased glucose utilization (FDG-PET imaging), Tau hyperphosphorylation, thinning of the cortex and decreased hippocampal volume precedes cognitive dysfunction.

One of the first brain regions to be affected early on in AD is the hippocampal-entorhinal circuit. However, very little is known about those interconnected neural networks which project to these areas which might actually be causal or could hamper neuronal processing and thus initiate the hippocampal-entorhinal system dysfunction. The ideal candidates in this scenario are the neurotransmitter systems which project to these regions specially the locus coeruleus - noradrenergic system or the LC-NA system located in the brainstem. LC axons innervate almost all the structures that are preferentially involved in the progression of the disease including hippocampus and cortex. Our lab seeks to understand the circuit mechanisms involving LC that are perturbed early in AD and trigger/orchestrate degeneration progressively. We use transgenic mice as a model system carrying familial AD mutations which mimic the pathological and behavioural hallmarks of the disease. The model allows us to ask specific questions about the underlying biology of AD progression. Further, we also use quantitative behavioral assays relevant to the symptoms of AD such as spatial reference memory task (Morris Water Maze), working memory task (Radial Arm Maze), episodic memory task (Object-place-context recognition tasks) and attentional set-shifting task. We further combine these quantitative behavioural assays with viral tracings and manipulation of genetically defined cell types such as LC neurons using pharmacogenetics to causally assess the contribution of individual circuit elements to a particular aspect of behavioural output. The combination of these approaches enables us to delineate the role of defined circuit elements in the initiation and progression of AD.



Smitha Karunakaran, PhD
Assistant Professor at the Centre for Brain Research

Dr. Karunakaran received her degrees from Kasturba Medical College (MSc. Medical Biochemistry, 2000) and National Brain Research Centre (PhD. 2009). Her PhD was focused on the molecular mechanisms underlying the selective neuronal vulnerability in Parkinson’s Disease. She completed her postdoctoral training at the Friedrich Miescher Institute (FMI) in Basel studying the neural circuit mechanisms involved in long term memory consolidation. She joined CBR in 2017, where her laboratory now employs multidisciplinary approaches to study how early perturbation in fundamental neuronal circuits contribute to the early cognitive symptoms in Alzheimer's disease.

Present Lab Members

ruchikaRuchika Mahesh Agarwal
M.Sc (Medical Biotechnology)
Biochemistry Dept, Maharaja Sayajirao University, Baroda, Gujarat.
Designation: Project Assistant
Currently working on "Hippocampal circuitry in early Alzheimer’s Disease"

Former Lab Members

jessicaShanice Jessica Hermon
Integrated M.Sc Student
School of Biological Sciences, NISER, Bhubhaneswar.
Designation: Summer Intern
Currently working on "Hippocampal circuitry in early Alzheimer’s Disease"

rubyRuby Gupta
Integrated M.Sc.,Life Sciences, Centre for Life Sciences,
Central University of Jharkhand, Jharkand.
Designation: Project Assistant
Currently working on "Hippocampal circuitry in early Alzheimer’s Disease"


  1. Kommaddi RP, Das D, Karunakaran S, Nanguneri S, Bapat D, Ray A, Shaw E, Bennett DA, Nair D, Ravindranath V. ABeta mediates F-actin disassembly in dendritic spines leading to cognitive deficits in Alzheimer's disease. J Neurosci. 2017 Dec 15: 2127-17. PMID:29246925

  2. Karunakaran S, Chowdhury A, Donato F, Quairiaux C, Michel CM, Caroni P. PV plasticity sustained through D1/5 dopamine signaling required for long-term memory consolidation. Nat Neurosci. 2016 Mar;19(3):454-64. PMID:26807952.

  3. Ray A, Sehgal N, Karunakaran S, Rangarajan G, Ravindranath V. Dopaminergic toxin MPTP activates ASK1-p38 MAPK death signaling pathway through TNF-dependent thioredoxin oxidation in Parkinsonism mouse model. Free Radic Biol Med. 2015 Oct; 87: 312-25. PMID: 26164633.

  4. Saeed U, Karunakaran S, Meka DP, Koumar RC, Ramakrishnan S, Joshi SD, Prakash N, Ravindranath V. Redox activated MAP kinase death signalling cascade initiated by ASK1 is not activated in female mice following MPTP - novel mechanism of neuroprotection. Neurotox Res. 2009 Aug; 16(2): 116-26. PMID: 1952628

  5. Karunakaran S and Ravindranath V. Activation of p38 MAP kinase in the substantia nigra leads to nuclear translocation of NF-kB in MPTP treated mice: Implication in Parkinson's disease. J Neurochem. 2009 May 11; 109(6): 1791-1799. PMID: 19457134

  6. Karunakaran S, Saeed U, Mishra M, Valli RK, Joshi SD, Meka DP, Seth P, Ravindranath V. Selective activation of p38 MAP kinase in dopaminergic neurons of substantia nigra leads to nuclear translocation of p53 in MPTP treated mice. J Neurosci. 2008 Nov 19; 28(47): 12500-12509. PMID: 19020042

  7. Karunakaran S, Saeed U, Ramakrishnan S, Koumar RC, Ravindranath V.Constitutive expression and functional characterization of mitochondrial glutaredoxin (Grx2) in mouse and human brain. Brain Res. 2007 Dec 14; 1185:8 - 17. PMID: 17961515

  8. Karunakaran S, Diwakar L, Saeed U, Agarwal V, Ramakrishnan S, Iyengar S, Ravindranath V. Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death-associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson's disease: protection by alpha-lipoic acid. FASEB J. 2007 Jul; 21(9): 2226 - 36. PMID: 17369508



Centre for Brain Research
SID (Innovation centre) complex
Indian Institute of Science (IISc)
Malleswaram 18th Cross
Karnataka, INDIA.

Email: smitha[at]iisc.ac.in