Neural basis of active sensation: Role of primary afferents

Touch and vision are both active senses: we investigate objects by sweeping our hands across them; we investigate the environment by scanning our eyes across it. Similarly, the whisker system of rats and mice is an active sense: these animals explore their environment by rhythmically sweeping their whiskers backwards and forwards ('whisking'). Rodents can tell the location of an object very accurately using their whiskers, but only if they can actively move them. Since it is well-established that different sensory systems in different mammals have profound similarities, studying whiskers can offer important insight into general questions about the brain mechanisms of perception.

Most of our current knowledge of the whisker system has come from work on anaesthetised animals. This approach continues to be useful for certain questions but, in an anaesthetised animal, the muscles that control whisker movements are still. To fully understand an active sensory system, it is crucial to study awake, behaving animals. However, in the past it was very difficult to accurately measure precisely how individual whiskers move in an awake animal. Now, however, new methods have been developed that overcome this difficulty. For the first time, it is possible to precisely measure how the whiskers of an awake rat/mouse are moving whilst, at the same time, measuring the electrical activity of the relevant individual brain cells.

Surprisingly, there are basic issues about how the very first stage in the whisker system operates in the awake animal, that are not understood. The nerve cells at this first stage are known as 'primary whisker afferents'. In this project, the specific questions we want to answer are as follows. In an awake mouse, what information do the primary afferents convey about whisker movements to the brain? Is the information that primary afferents provide reliable, or can afferent 'noise' account for the errors that animals make in perceptual tasks? We will investigate these questions by using a video speed, high resolution video camera to measure precisely how the whiskers are moving at the same time as we measure the activity of primary afferents from the brain. The proposed experiments will reveal what the input to the brain is under active perception conditions. This research will provide basic knowledge that is pertinent to the effort to develop 'neuroprosthetic devices' to replace damaged nerves (e.g., diabetic neuropathy).

With the help of our collaborator K. Svoboda (Janelia Farm), we have established state-of-the-art techniques in Manchester to correlate precisely the motion of a whisker with the activity of the associated neurons in the somatosensory pathway, in the awake animal. It is now feasible to address basic questions concerning active perception that were previously intractable.

The awake state differs from the anaesthetised state in important ways. In the awake state, mechanoreceptors are subject not only to external forces on the whisker shafts but also to internal forces from the facial muscles that control whisking. Thus, there is a long-standing issue concerning the extent to which hypotheses concerning primary afferent function derived from work on anaesthetised animals are applicable to the awake state. Which features of whisker motion (angle, angular velocity, curvature) do primary afferents respond to? How do primary afferents represent sensory information in a whisker-guided discrimination task? How does primary afferent activity drive the animal's behavioural choice?

We propose to address these questions by recording action potentials fired by individual primary afferents in awake, head-fixed mice using microelectrodes implanted in the trigeminal ganglion. Simultaneously, whisker movements will be precisely measured using high-speed, high-resolution video. Thanks to interaction with our collaborator, K. Svoboda (Janelia Farm), we have established the necessary equipment and have preliminary data demonstrating feasibility of the proposed experiments. This is the first time that these techniques have been applied to the ascending whisker system. Due to the complexity of the data, a cross-disciplinary approach that combines experiment with neuroinformatics is valuable. Our extensive track record with both whisker system and neuroinformatics makes us uniquely well-placed to carry out this project.

The expected outcome from this research is insight into the fundamental neuroscience problem of the neural basis of perception. In the long-term, advances in basic science research is crucial for providing the knowledge base from which translational scientists of the future can develop novel treatments. Our work on primary afferents has direct potential for impacting on diseases of the peripheral nerves (e.g., diabetic neuropathy) and also on efforts to develop neuroprosthetic devices that aim to replace damaged sensory organs.

The immediate priority over the 3-year time-scale of the project is ensure that as large as possible a community of basic and clinical neuroscientists are informed about the research. To this end, we will communicate our findings as broadly as possible by publication in the highest impact journals possible and by communicating the findings at the most widely attended conferences.

In the area of neurobiologically inspired intelligent systems (NBIS), there is significant interest in whisker-guided robotics (e.g., the EU FP7 BIOTACT project). Our work on primary whisker afferents will give insight into what the input to the brain is during whisker-guided behaviour and is likely to be of interest to this community. Again, the immediate priority over 3 years, is to communicate the findings as widely as possible. To address this, we will communicate our findings also at conferences attended by researchers interested in NBIS (the Computational Neuroscience Meeting, the Cosyne Meeting).