Final Activity Report Summary - DENDRITES AND MEMORY (Behavioural roles for information processing in the dendrites of cortical neurons)
Neurons in the brain have ornate dendrites that are the target of thousands of synaptic inputs. In each neuron the many synaptic responses in dendrites are integrated to produce a single output from the axon. Although there is increasingly detailed understanding of the physiological and molecular properties of dendrites, little is known about how dendritic integration of neuronal activity influences behaviour. This issue is particularly important as the complex electrical properties of dendrites may greatly expand the repertoire of computations that the brain can perform and as many common brain disorders are increasingly recognised to involve deficits in the integration of neuronal activity. The research team developed new tools to test the hypothesis that different components of dendritic integration by cortical neurons play distinct roles in forms of memory that require the hippocampus. The research team developed a tool box of viral vectors to manipulate ion channels found in dendrites. The tool box was built using a modular systems that enables individual components to be easily re-used. Components included promoters for neuronal expression, ion channels, optogenetic tools, fluorescent proteins and artificial microRNAs.
To explore functional roles of dendritic integration the research team used electrophysiological and behavioural techniques in combination with viruses developed using the tool box and with conventional genetically modified mouse lines. The teams major findings include discovery of new principles for organisation of dendritic integration by neurons in the medial entorhinal cortex, contributions to understanding the molecular basis for action potential initiation by neurons in the cerebellum, development of a powerful new in vivo model for investigating the long-term consequences of manipulating integrative properties of neurons, establishment of cell-type specific roles for ion channels important for dendritic integration and demonstration of cell-type specific behavioural roles for these ion channels. In doing this work the research team has contributed to understanding of the principles through which integration of neuronal activity in the dendrites of cortical neurons contributes to learning and memory. Parts of the work have already been published in major international journals and further manuscripts will be submitted in the coming months.
The team members were recruited from diverse technical backgrounds - molecular biology, behaviour, electrophysiology - and several countries of origin - US, Italy and UK. The team members training included acquiring new technical skills from their colleagues, organising, speaking and participating in international workshops, presentation of work at conferences, writing manuscripts for publication of work, and contributing to the planning and design of successful applications for further funding.
To explore functional roles of dendritic integration the research team used electrophysiological and behavioural techniques in combination with viruses developed using the tool box and with conventional genetically modified mouse lines. The teams major findings include discovery of new principles for organisation of dendritic integration by neurons in the medial entorhinal cortex, contributions to understanding the molecular basis for action potential initiation by neurons in the cerebellum, development of a powerful new in vivo model for investigating the long-term consequences of manipulating integrative properties of neurons, establishment of cell-type specific roles for ion channels important for dendritic integration and demonstration of cell-type specific behavioural roles for these ion channels. In doing this work the research team has contributed to understanding of the principles through which integration of neuronal activity in the dendrites of cortical neurons contributes to learning and memory. Parts of the work have already been published in major international journals and further manuscripts will be submitted in the coming months.
The team members were recruited from diverse technical backgrounds - molecular biology, behaviour, electrophysiology - and several countries of origin - US, Italy and UK. The team members training included acquiring new technical skills from their colleagues, organising, speaking and participating in international workshops, presentation of work at conferences, writing manuscripts for publication of work, and contributing to the planning and design of successful applications for further funding.