Final Report Summary - HIPPOCHRONOCIRCUITRY (The chronocircuitry of the hippocampus during cognitive behaviour)
The mammalian cerebral cortex represents the pinnacle of the evolutionary process of life as to this day. The cerebral cortex allows us to perform complex cognitive processes such as the subjective interpretation of the world, coding and retrieval of memories, expression of emotions, understanding and empathizing with other individuals, and scientifically investigating the universe including brain. Time is the key metric to all cortical operations driving the selection for computational sophistication and the evolution of neuronal diversity. As a result the cerebral cortex of mammals has an enormous diversity of cells operating in synaptic circuits. The hippocampus is an area of the cerebral cortex contributing to the encoding and retrieval of spatial and episodic memory, processing of emotions and contributes to certain types of learning. Hippocampal neurons can be divided into excitatory pyramidal cells, which use glutamate as a neurotransmitter and give both local and long-range axonal projections, and inhibitory interneurons, which are GABAergic and control the activity and timing of pyramidal cells mainly through local axons. Both types of neuron can be further subdivided on the basis of their distinct axo-dendritic arborisations, subcellular post-synaptic targets, firing patterns and by their differential expression of signalling molecules, including receptors, ion channels, neuropeptides, transcription factors and Ca2+ binding proteins.
In this project we have established a novel technique that allows the recording and labelling of identified neurons during free behaviour and without the influence of drugs or anaesthesia. Using this technique we have been able to show how distinct types of GABAergic interneuron make differential contributions to the hippocampal representations during behaviour. We found that parvalbumin-expressing basket cells, making synapses onto the cell bodies and dendrites of pyramidal cells, dynamically change their firing according to the ongoing behavioural state including running, sleep and quiet wakefulness. In contrast, ivy cells, which provide also extrasynaptic modulation of pyramidal cells, fire with similar activity throughout different behaviours to provide homeostasis to the hippocampal network. In addition, bistratified and O-LM cells, targeting different sections of the dendritic tree of pyramidal cells, provide well-timed inhibition for the generation of network synchrony and operations. Also, using a novel optogenetic technique, we demonstrated that pyramidal cells in the ventral hippocampus route different types of information selectively to distinct target areas: Pyramidal cells which project to the prefrontal cortex convey preferentially information about anxiety and other pyramidal cells projecting to the nucleus accumbens carry enriched information about goal locations. Our data demonstrate how distinct types of neuron differentially organise information-processing in the working brain.
In this project we have established a novel technique that allows the recording and labelling of identified neurons during free behaviour and without the influence of drugs or anaesthesia. Using this technique we have been able to show how distinct types of GABAergic interneuron make differential contributions to the hippocampal representations during behaviour. We found that parvalbumin-expressing basket cells, making synapses onto the cell bodies and dendrites of pyramidal cells, dynamically change their firing according to the ongoing behavioural state including running, sleep and quiet wakefulness. In contrast, ivy cells, which provide also extrasynaptic modulation of pyramidal cells, fire with similar activity throughout different behaviours to provide homeostasis to the hippocampal network. In addition, bistratified and O-LM cells, targeting different sections of the dendritic tree of pyramidal cells, provide well-timed inhibition for the generation of network synchrony and operations. Also, using a novel optogenetic technique, we demonstrated that pyramidal cells in the ventral hippocampus route different types of information selectively to distinct target areas: Pyramidal cells which project to the prefrontal cortex convey preferentially information about anxiety and other pyramidal cells projecting to the nucleus accumbens carry enriched information about goal locations. Our data demonstrate how distinct types of neuron differentially organise information-processing in the working brain.