Current research on neurotransmission in the cerebral cortex is heavily biased towards rodents for understandable reasons. The tissue is easily accessible for experimentation, there is a wealth of accumulated knowledge and we have the ability now to probe the function of individual proteins with transgenic and optogenetic technology; after all, the rodent is a mammal too, with a six layered cortex, pyramidal cells and interneurons, just like us. However, the cerebral cortex is the seat of higher cognitive function and consciousness and is considerably larger and probably more highly evolved in humans compared even to non-human primates, therefore understanding how it works requires the direct study of human, as opposed animal models. Although there have been many studies of neuropathology in post mortem tissue, invasive studies of normal and living human brain remain rare, and we felt they needed to be promoted.
Thus, with the sponsorship of the Anatomical Society, we organised a symposium, entitled ‘GABAergic neurotransmission in the human cerebral cortex: Same rules apply?’ as part of the British Neuroscience Association 2013 Festival of Neuroscience, London, 7–10th April, 2013, bringing together four speakers who have tackled directly the problem of studying neural circuitry and neurotransmission in the human brain with a number of approaches. Dr Gavin Clowry (Newcastle University) chaired the session and has provided a review article which considers whether humans have more and different types of GABAergic cortical interneurons, with differences in function, than our model species, and whether this expanded repertoire of functional types has been matched by a co-evolution of their developmental origins.
The first speaker, Prof Gabor Tamas (Szeged University) described his work using both electrophysiological and anatomical approaches to study the role of GABAergic neurotransmission in cortical microcircuits in living slices from human brain. He described how a subset of connections from pyramidal cells to fast-spiking interneurons is selectively strengthened in the human cortical circuit, helping them to pass on longer sequences of information. He also described studies characterising the gene expression profile of individual interneurons. Dr Mark Cunningham (Newcastle University) also uses human in vitro preparations to study the generation of gamma (30-80 Hz; γ) frequency oscillations in neocortical slices from both epileptic subjects and non-epileptic comparisons and further analysing the tissue for expression of interneuron markers. Patterns of activity were compared with in vivo EEG recordings, and computer simulated models derived from animal experiments.
Prof Rodrigo Quiroga (Leicester University) described how to make recordings from individual neurons in patients implanted with electrodes for clinical reasons. He gave an entertaining presentation about ‘concept cells’; neurons in the human medial temporal lobe with selective and invariant responses that represent the meaning of a stimulus and discussed their proposed role in declarative memory. With his colleagues he has provided a review of how to undertake such studies including a guide to processing collected data. Finally Professor Krish Singh (Cardiff University) spoke about non-invasive functional brain imaging and the relationship between the BOLD response, measured by fMRI and oscillatory power changes in the cortex, as measured with MEG. He described using these approaches to elucidate the role of GABAergic neurotransmission in determining oscillatory dynamics and performance on behavioural tasks. With his colleagues he has provided a research paper exploring structural and neurochemical correlates of differences in γ frequency oscillations in human visual cortex.
Our hope is that anyone who attended the symposium, or reads this report and the accompanying articles, will be inspired to include direct study of living human neurons as part of their research, because we firmly believe that we will never the understand the human brain in all its full complexity unless we can study it directly.