Multiple lines of evidence support these conclusions: pathological amnesia in Alzheimer’s disease is associated with degeneration of the hippocampus and neighbouring regions; experimental lesions of the hippocampus leave rats and mice unable to learn and remember where hidden food is buried; and functional brain imaging in healthy taxi drivers shows the hippocampus becoming active as they recall tortuous routes through the London traffic. But next time you find yourself staring at the back of a taxi driver’s head, remember that as well as learning and remembering all those routes, he needs to be processing all the visual information rushing through the windscreen, following the commands you bark from the rear seat, obeying road traffic regulations, controlling the sharp jabs of his feet on accelerator and brake, and chatting excitedly about the latest football results. All that takes a lot of brain, and the simultaneously active specialised brain structures that deal with vision, hearing, rule learning, movement, language and emotion must somehow co-ordinate their activities and interactions with one another.
Decoding how these networks of neurons are co-ordinated across multiple brain regions during complex functions and behaviour presents a challenge at the forefront of neuro-scientific research. Our approach to addressing this challenge is relatively direct: we use bundles of extremely fine electrodes to record the electrical activity produced by hundreds of neurons in the brains of rats and mice as they perform ‘taxi-driver’ tasks while navigating their way around mazes in search of chocolate. The electrodes used are approximately 15 micrometers in diameter (the average human hair is about 100 micrometers), and up to 128 of them can be monitored simultaneously, 32,000 times per second. Since these electrodes can record simultaneously from multiple neurons in multiple brain structures, this technology allows us to detail the fundamental nature of the neuronal activity and interactions underlying behaviour.
Where was that restaurant I dined in last night?
A striking feature of neuronal activity in the hippocampus as these rats and mice run around mazes is its rhythmicity: individual neurons tend to fire short, high-frequency bursts of activity about ten times per second (10 Hz). Furthermore, populations of hippocampal neurons become co-ordinated with one another on this timescale, leading overall hippocampal activity to oscillate at about 10 Hz – this is known as the ‘theta rhythm’. The brain’s net electrical activity can be recorded through electrodes on the scalp, and is known as the electroencephalogram (EEG). Like in rats, the theta rhythm in human EEG recordings becomes prevalent as volunteers perform learning tasks, or navigate around the virtual mazes common in computer games. In fact, human and rodent EEG recordings share many common motifs, including a range of 1-200 Hz rhythms that become prominent in different brain regions and during different types of behaviour and sleep. But are all these brain waves important, or simply phenomenological ripples?
Using multi-neuron recordings in trained rats, we recently demonstrated that the hippocampal theta rhythm becomes synchronised with rhythmic activity in another specialised brain structure – the prefrontal cortex – when rats approach a decision point on a maze. In fact, just by examining the degree of hippocampal-prefrontal synchrony, we were able to predict whether the rat was about to make the right choice (and win his chocolate) or make a mistake. We hypothesised that theta rhythm synchrony allowed neurons in the prefrontal cortex to ‘borrow’ information from the hippo-campus, which was subsequently used to guide the rats’ decisions.
This is one of many laboratory and clinical observations which suggest that synchronous brain rhythms reflect, or underlie, functional interactions within and between neuronal populations. Neuronal oscillations therefore present a tantalising target for both reading and shaping brain activity. For example, EEG activity can be used as a signal to control prosthetic limbs, and a recent study in Germany showed that rhythmical stimulation of volunteers’ brains during sleep improved their memories of previously learned facts.
But what of our own mental health?
If the normal brain is complicated, the diseased brain challenges neuro-scientists yet further. Most psychiatric disorders cannot be explained by overt pathology in a single brain region, but arise as a consequence of dysfunctional interactions between brain regions. Schizophrenia – which afflicts up to one per cent of the world’s population – is thought to involve dysfunctional interactions between the hippocampus and the prefrontal cortex, and similar principles are likely to apply to depression and Attention Deficit Hyperactivity Disorder. All these disorders are associated with abnormal neural synchrony and EEG oscillations, but the molecular and cellular bases of these abnormalities are not known; successful treatments therefore remain elusive.
This is where our neuronal network recordings in rodents come to the fore: measuring co-ordinated, rhythmic activities between the hippocampus and prefrontal cortex in rat and mouse models of schizophrenia constitutes a test system with which to define the cause of the disease and investigate novel therapies. Deciphering the mechanisms and roles of co-ordinated neural activity is therefore fundamental not only to our understanding of normal brain function, but also to the development of animal models of psychiatric disorders, with the ultimate goal of clinical diagnosis and treatment of brain disease in humans.
But what of your own mental health? Well, be sure to compliment taxi drivers on their remarkable feats of neuronal co-ordination. And don’t push swords up your nose.