lindaunobelMadhurima Benekareddy is a 27-year-old researcher standing at the cross-roads of psychology and neuroscience. She researches the effects of trauma on the brain in its delicate stages of development, when we are children and adolescents, at the Tata Institute of Fundamental Research in Mumbai, India. The young brain is more plastic, and therefore can be particularly badly affected by negative – or positive – events. Trauma can even be passed down the generations. Benekareddy’s area of study focuses on serotonin receptors in the brain. Benekareddy’s work should interest all of us, especially parents.
I catch up with Benekareddy over email just as the 61st Meeting of the Nobel Laureates in Lindau begins to kick off. I will find her later in the week and see how she is getting on, what she is learning, and what she is enjoying. In the meantime, you can read her answers to my questions:
About Benekareddy’s work:
Q: What kind of life events can affect the brain?
An accumulating body of evidence from human and animal studies indicates that a variety of stressful and enriching experiences mould brain function. Work from rodent models has examined the effect of life events on brain structure and function in the sensory and emotional systems in the brain. Adverse experiences in adulthood like chronic adult stress, trauma lead to structural brain alterations in specific brain regions and also cause adverse effects on function. Exposure to an enriched environment or voluntary exercise on the other hand has been shown to cause improved brain function.
Postnatal and adolescent experiences have a more dramatic and long lasting influence than events in adulthood.
Stressful events in early postnatal life increase the risk for mental disorders like depression, anxiety, schizophrenia and so on in adulthood. Individuals with a history of early stress show deficits in stress coping in response to a subsequent stressor in adulthood. Enriched environment during adolescence can reverse the adverse effects of early life stress on brain function. It is hypothesised that these stressors impinge on the normal developmental trajectory of the brain leading to aberrant structural and behavioural output.
Q: Why are serotonin receptors important?
Several neural mechanisms have been implicated in mediating the role of experience in shaping neural circuits. The neurotransmitter serotonin has been shown to be a major player in mediating the effects of stress on the brain. Knockouts of serotonin 1A and 2A receptor have been shown to have deficits in normal anxiety and fear responses.
Serotonergic neurotransmission is vital in early life for normal brain function. Early studies with knockout mice with elevated serotonin levels exhibit a loss of normal organisation of the somatosensory cortex. In addition, administration of drugs that increase serotonin levels to rat pups leads to robust alterations in depressive-like and anxiety behaviors throughout life. Our own results show that blockade of the serotonin 2A receptors during the early stress of maternal separation can prevent the adverse effects in a model of early stress. However it is clear that different serotonergic receptors have different and sometimes opposing effects on anxiety and depressive behaviours. The specific contribution of different serotonergic receptors in modulating the effect of experience on brain function remains an open question.
Q: Why do teens in particular have elevated brain plasticity?
The brain of a newborn has the broad layout and connectivity in place. However, the brain retains a great degree of plasticity until adolescence to facilitate fine tuning of circuitry based on experience. Neural activity that is based on experience plays a major role in this fine tuning. The emotional and cognitive framework of an individual is encoded by the complex interplay of environmental factors with the underlying genetic milieu. The biological substrate of this environmental programming of behaviour has been postulated to be the plasticity in brain structure. Such structural plasticity is of significant adaptive value in shaping behaviour to suit changing environmental demands.
However, traumatic life events like chronic stress, loss of a close family member could lead to maladaptive changes in brain structure and cause adverse alterations in adult behaviour. Owing to the extraordinary structural plasticity seen during this period, adverse life events can impinge upon the development of neural circuits to cause lasting alterations in emotional and cognitive behavior.
Such developmental sensitive critical periods have been well studied in the sensory systems. Recent evidence obtained from studying the children from the Romanian orphanages and rodent models of adverse early experience points to the concept of critical periods in the development of emotional circuitry as well.
Q: What is effect of trauma on children’s behaviour?
Adverse experience like parental loss, neglect, or abuse during early life has been shown to be a potential risk factor for anxiety, depression, attention disorders, overactivity, social deficits, borderline personality disorders, and other affective disorders throughout life. Children growing up in foster care or in orphanages have been reported to exhibit abnormal diurnal rhythms of the stress hormone, cortisol. Studies investigating the effect of childhood abuse examined self reported retrospective scores of childhood sexual and physical abuse or loss of a parent as a risk factor for subsequent vulnerability to depressive, anxiety, panic disorders and substance abuse in adulthood. Adults, especially women with a history of sexual abuse have also been reported to exhibit dysregulated stress response.
Q: How can you prevent damaging the serotonin receptors as a consequence of trauma? What do you think are the implications for parenthood?
The serotonin 2A receptor function is elevated as a result of early life stress in a rodent model and blocking this receptor during the stress prevents the adverse effects of this stress on anxiety like behaviour. However, we are currently trying to understand if environmental manipulations like increased tactile stimulation or enriched environment can be also used to intervene during stress.
Q: How can the effects of trauma on the brain be carried down generations? What particular genes are implicated in this?
The effect of trauma is transmitted across generations via epigenetic marks on specific genes. While it is not understood what are the genes involved in such a phenomenon, recent work from Michael Meaney’s group implicates the glucocorticoid gene (receptor for the stress hormone coricosterone) as a target of such epigenetic modifications.
Q: How did you get into your field of research?
I got into research by way of a high school summer project which I presented at an international science fair. Just the buzz of being in a large scientific group sharing ideas and discussing projects, with like minded students from all over the world, so early on in my life, changed my trajectory. Since then, I have been starry eyed about research and eventually after my undergraduate degree in science, applied to a integrated PhD program at the department of biological science at Tata Institute of Fundamental Research (TIFR). I was broadly interested in neuroscience and rotated in neuroscience labs at TIFR and was fascinated by some of the models that Dr. Vidita’s lab works on.
Q: What is it like working at Tata Institute of Fundamental Research and in Mumbai?
Being a graduate student in TIFR was extremely enjoyable. We have an intellectually charged environment, excellent funding opportunities, relatively less bureaucracy, and plenty of opportunities to travel to scientific meetings and collaborate with labs from all around the world. Being an institute aimed at fundamental research, TIFR also encourages basic research. Being in an interdisciplinary environment with students from other cultural and academic backgrounds is also very enriching.
Q: Where is your dream lab? And what is it like? What are the people like?
My dream lab is that of Dr. Robert Sapolsky. He used to do some field work studying the social hierarchy of monkeys in the wild.
Q: What are you proudest of in your career?
I don’t think that moment is here yet. But being selected for the Lindau meeting definitely comes close.
Q: What do you find most challenging about your work?
I think designing the right experiment to ask a question can be challenging some times. Especially given the complexity of the brain, there are several possible hypotheses and picking the right one is always a tough call and one that requires a lot of thought and intuition.
Q: Who are you most looking forward to meeting at Lindau? Who is your science hero or heroine?
I am really looking forward to talking to Prof. Dr. Torsten Nils Wiesel. He has done pioneering work in understanding the organisation of the visual system.