Identified prefrontal neurons in a working memory task

The mammalian prefrontal cortex supports and generates complex cognitive computations and behaviour including the encoding and retrieval of working memory, executive control and decision making as well as the encoding of abstract representations and rules to guide problem solving and solution-orientated behaviour. The prefrontal cortex contains a large diversity of distinct types of neurons, which interact through synaptic circuits, to perform the neuronal computations necessary for cognitive behaviours. In this project we will determine the activity patterns of identified types of neuron in the medial prefrontal cortex while rats will perform a delayed-cue-matching-to-place task. In this working memory/decision making task, animals will learn to associate different stimuli with different behavioural actions. The rats will run on a Y maze and will receive a chocolate or a cherry juice stimulus and will have to keep the information of this stimulus in their working memory during a delay period, before they can decide to turn left or right according the type of the previous stimulus; they will receive a reward only if they turn right following a cherry stimulus or left following a chocolate stimulus. We will record the activity of distinct types of prefrontal pyramidal cells and interneurons using our recently developed juxtacellular recording and labelling technique in freely moving rodents. This will allow us to unequivocally determine the type of the recorded neurons using post-hoc histological analysis of molecular expression profiles tested with immunohistochemistry, position and arborisation of recorded cell bodies, dendrites and axons visualized in 3D with neurolucida reconstruction, as well as electron microscopic verification of subcellular target domains of the labelled axons. In addition we will detect various network oscillations the prefrontal cortex during task performance and we will determine how distinct types of neuron contribute to these brain waves. The experiments performed during this project aims to test the hypothesis that distinct types of prefrontal neurons contribute differentially to the neuronal operations underlying a working memory/decision making task. Furthermore, the detected firing patterns and identified synaptic circuits will provide insights into the cellular mechanisms of cognitive computations in the prefrontal cortex.

In this project we could show how networks of prefrontal neurons cooperate to contribute to working memory and decision making. The mammalian prefrontal cortex supports and generates complex cognitive computations and behaviour including the encoding and retrieval of working memory, executive control and decision making as well as the encoding of abstract representations and rules to guide problem solving and solution-orientated behaviour. The prefrontal cortex contains a large diversity of distinct types of neurons, which interact through synaptic circuits, to perform the neuronal computations necessary for cognitive behaviours. In this project we determined the activity patterns of identified types of neuron in the medial prefrontal cortex during a delayed-cue-matching-to-place task. In this working memory/decision making task, different sensory stimuli have to be associated with distinct behavioural actions. However, those actions have to be delayed by a certain amount of time and the information has to be kept in the working memory for successful task performance. We recorded the activity of distinct types of prefrontal pyramidal cells and interneurons using our recently developed juxtacellular recording and labelling technique. This allowed us to unequivocally determine the type of the recorded neurons using post-hoc histological analysis of molecular expression profiles tested with immunohistochemistry, position and arborisation of recorded cell bodies, dendrites and axons visualized in 3D with neurolucida reconstruction, as well as electron microscopic verification of subcellular target domains of the labelled axons. In addition we detected various network oscillations the prefrontal cortex during task performance and we determined how distinct types of neuron contribute to these brain waves. Our results showed that ensembles of prefrontal principal cells and interneurons differentiate their activity for different task episodes as well as different decisions. We found that the recruitment of individual neurons into ensembles with different firing patters were dependent on their input and output connectivity, which varied between different cell types. Because the specific firing patterns of these cells were strongly impaired during the performance of the task without cognitive content, we concluded that the different firing patterns of distinct types of prefrontal neuron support the storage of working memory and differentiation of behavioural options over a sequence of behavioural actions.