The Lonely brain

Dr Samuel Barnes Ph.D is a Lecturer at Imperial College London in the Division of Brain Sciences and was recently awarded a UK Dementia Research Institute Fellowship. The goal of his research is to understand the role of neural circuit plasticity in aging and neurodegeneration. His group uses a combination of in vivo voltage and calcium imaging, bioelectronics and electrophysiology to investigate the neural plasticity factors that make the aged brain susceptible to neurodegeneration and ultimately dementia. You can read more about his work here.  He will be speaking at the Loneliness in Older People and its Impact on Health event on 13 June at Wellcome Collection in London.

Daydreaming can be one of life’s great pleasures. Losing yourself in a thought or spending time quietly reflecting on the day’s events is an important part of modern life. But what if solitary thought was the only option? For many older people periods of loneliness are all too frequent. Such periods of social isolation can involve little to no contact with people for prolonged periods of time. What do these prolonged stretches of loneliness do to the brain?

To answer this question, we must consider how the brain processes the sensory and social world. The substrate of thought is the electrical activity that flows between neurons in the brain. These tiny nerve cells are connected to each other forming complex circuits that store and process sensory experience.Such neural circuits are not hard-wired but instead possess the remarkable ability to reorganise and refine their architecture long into adulthood (Barnes and Finnerty, 2010). This adaptive ability is known as neural plasticity and is thought to be central to the storage and recall of memories. The degree of neural plasticity expressed by the brain declines in later life (Burke and Barnes, 2006). This decline in function has been proposed as a factor that may increase the susceptibility of the aged brain to neurodegeneration (Mesulam, 1999). Social isolation may exacerbate the natural run-down of neural plasticity that occurs in later life and increase the risk of developing dementia (Livingston et al., 2017).

Social isolation can be an issue regardless of age but older people are more vulnerable for a variety of reasons including, reduced mobility, a general decline in health and the end of daily working relationships (Díez et al., 2014; Hand et al., 2014). The exact mechanisms by which social isolation influences neural plasticity have yet to be fully elucidated. Work using both aged mice and mice that model certain features of neurodegeneration have begun to define key molecular and cellular processes that are sensitive to social isolation, but how larger networks of neurons that coordinate complex behaviours are influenced by social isolation remains unclear (Hsiao et al., 2011; Huang et al., 2015).

To address this question, my group utilises new technology that combines light microscopy with advances in mouse genetics to ‘look’ at the activity of neurons in the living mouse brain. We make optical recordings of both neural activity and the plasticity expressed at synapses – which are the contact points that allow neurons to communicate with each other (Sammons et al., 2018). Using this data we can begin to identify the neural circuit maps that underpin cognition and then piece together how factors such as social isolation perturb these circuits in the aged brain. Understanding how social isolation changes the properties of neural circuits in this level of detail may even present the opportunity to reverse the effects of social isolation and reboot neural plasticity in old age.

Register for Loneliness in Older People and its Impact on Health event on 13 June at Wellcome Collection in London

Related reading:

• Barnes, S.J., and Finnerty, G.T. (2010). Sensory experience and cortical rewiring. Neurosci. Rev. J. Bringing Neurobiol. Neurol. Psychiatry 16, 186–198.
• Burke, S.N., and Barnes, C.A. (2006). Neural plasticity in the ageing brain. Nat. Rev. Neurosci. 7, 30–40.
• Díez, E., Daban, F., Pasarín, M., Artazcoz, L., Fuertes, C., López, M.J., and Calzada, N. (2014). [Evaluation of a community program to reduce isolation in older people due to architectural barriers]. Gac. Sanit. 28, 386–388.
• Hand, C., McColl, M.A., Birtwhistle, R., Kotecha, J.A., Batchelor, D., and Barber, K.H. (2014). Social isolation in older adults who are frequent users of primary care services. Can. Fam. Physician Med. Fam. Can. 60, e322, e324-329.
• Hsiao, Y.-H., Chen, P.S., Chen, S.-H., and Gean, P.-W. (2011). The involvement of Cdk5 activator p35 in social isolation-triggered onset of early Alzheimer’s disease-related cognitive deficit in the transgenic mice. Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol. 36, 1848–1858.
• Huang, H., Wang, L., Cao, M., Marshall, C., Gao, J., Xiao, N., Hu, G., and Xiao, M. (2015). Isolation Housing Exacerbates Alzheimer’s Disease-Like Pathophysiology in Aged APP/PS1 Mice. Int. J. Neuropsychopharmacol. 18, pyu116.
• Livingston, G., Sommerlad, A., Orgeta, V., Costafreda, S.G., Huntley, J., Ames, D., Ballard, C., Banerjee, S., Burns, A., Cohen-Mansfield, J., et al. (2017). Dementia prevention, intervention, and care. Lancet Lond. Engl.
• Mesulam, M.M. (1999). Neuroplasticity failure in Alzheimer’s disease: bridging the gap between plaques and tangles. Neuron 24, 521–529.
• Sammons, R.P., Clopath, C., and Barnes, S.J. (2018). Size-Dependent Axonal Bouton Dynamics following Visual Deprivation In Vivo. Cell Rep. 22, 576–584.