Short-latency auditory and somatosensory input to dopaminergic neurons

The ascending dopamine systems have their cells of origin in an area of the brain referred to as the ventral midbrain. From here, they send projections which innervate widespread areas of the forebrain. As a consequence, it is perhaps not surprising that the dopamine systems are implicated in a wide range of normal brain processes (for example certain types of learning) and clinical disorders (for example Parkinson's disease). Although we know much about the neurotransmitter dopamine, the function or purpose of the message which dopaminergic neurons (i.e. ones that use dopamine to communicate with other areas on the brain) convey to the forebrain remains elusive. Studies in animals have shown that dopaminergic neurons are activated when an animal is presented with unexpected sensory events ('stimuli') in a range of modalities which have important implications for the animal / for example when an animal is presented with food or a food related stimulus. At present, the two main theories concerning the content of the dopamine message are that it is specifically related to 'rewards' like food, or that it has a broader remit, telling the forebrain that something important or salient has happened without telling it what it is. How do we choose between these two? We believe that an important strategy for decoding the dopamine message is to identify and then elucidate the perceptual properties of the sensory pathways providing input to dopaminergic neurons, because these neurons can only pass on (albeit in processed form) the information they are given. We already have evidence that visual information is relayed to dopaminergic neurons via an evolutionarily primitive structure, the superior colliculus, more in keeping with the 'salience' than the 'reward' hypothesis, given that the colliculus is much better at telling the brain that something has happened than ir is at analysing its properties. However, our knowledge of the sensory control of dopaminergic neurons is still incomplete: in particular, we lack fundamental information about the sensory systems which provide auditory and non-noxious somatosensory information to these neurons. The overall objective of the present proposal will be to determine the source(s) of this information in the rat, using a unique combination of techniques. Firstly, we will use anatomical techniques to trace the connections to dopaminergic neurons arising from auditory and somatosensory structures: this will give us an initial indication of the potential sources of this information. Secondly, we will record the activity of dopaminergic neurons in the anaesthetised animal whilst the animal is presented with auditory and somatosensory stimuli. By manipulating the activity of the anatomically identified putatitive sources of auditory and somatosensory information (either increasing or decreasing activity by the injection of chemicals), and observing the effect of these manipulations on the activity of dopaminergic neurons responding to auditory and somatosensory stimuli, it will be possible to identify which sources seem to provide the requisite information. Finally, we will use a technique called electrochemistry to determine whether the changes in the responses of dopaminergic neurons to auditory and somatosensory stimuli which the above manipulations produce have an impact on the release of dopamine in the forebrain. The proposed experiments will provide essential information required to assess the nature and quality of the perceptual information available to dopaminergic neurons. As a consequence, the functional role of the message conveyed to the forebrain via the activation of these cells, which is at present a matter of considerable debate, will become appreciably clearer. A corollary of this is that, when the dopamine systems 'go wrong' in dopamine-associated disorders, the nature of the subsequent deficit will be clearer, potentially opening the way for new therapeutic interventions.

Dopaminergic neurons (DA) are activated at short latency by unexpected salient sensory stimuli in a range of modalities. Current theories suggest that the signal conveyed by DA neurons exclusively concerns reward, or that it has a broader remit, telling the forebrain that something salient has happened without telling it what it is. An important strategy for decoding the signal is to identify and then elucidate the perceptual properties of the sensory pathways providing input to DA neurons. Visual information is relayed to DA neurons via a subcortical structure, the superior colliculus (SC), more in keeping with the 'salience' than the 'reward' theory, since the SC can signal that something has occurred but is perceptually primitive. However, our knowledge of the sensory control of DA neurons is still incomplete: in particular, we lack fundamental information about the sensory systems which provide auditory and somatosensory information. The overall objective of the present proposal will be to determine the source(s) of this information, using a unique combination of neuroanatomy, electrophysiology and electrochemistry. The overarching objective of determining the source(s) of auditory and somatosensory information can be broken down into three smaller issues, and the specific aims of the project will be to address these issues: 1. Does the SC relay auditory and/or somatosensory information to DA neurons?; 2. What other structures, if any, also provide auditory and/or somatosensory information to DA neurons? 3. Do responses in DA neurons to auditory and somatosensory stimuli lead to changes in the release of dopamine in the neostriatum? The proposed experiments will provide essential information required to assess the nature and quality of the perceptual information available to DA neurons. As a consequence, the functional role of the signal conveyed to the forebrain via the activation of these cells will become appreciably clearer.