Prof. Dr. Feldmeyer (D)
Prof. Dr. Dirk
Prof. Dr. Dirk
Klinik für Psychiatrie and Psychotherapie
Universitätsklinikum RWTH Aachen
Institut für Neurowissenschaften & Medizin
Neocortical microcircuits: Role of excitatory feedback circuits within a barrel-related cortical column
The barrel cortex is characterised by a network of intra- and interlaminar synaptic connections that perform different tasks but are nevertheless interdigitated (Lübke & Feldmeyer, 2007). We have considerable experience in investigating the structural and functional properties of synaptic connections in the barrel-related neocortical column. So far, we have largely concentrated on synaptic connections within the so-called ‘canonical’ neuronal microcircuitry of sensory cortices. These connections link the major thalamo-recipient layer 4 spiny neurons with layer 5B pyramidal cell, the major output neurons via pyramidal cells in layer 2/3 (s. Fig. 4A; Douglas & Martin, 2004). However, we have recently begun to investigate synaptic connections between layer 4 (L4) spiny neurons and pyramidal cells in the cortico-thalamic projecting layers 5B and 6. These synaptic connections form the intracortical section of the thalamo-cortico-thalamic feedback loop, which signals cortical activity back to the thalamus.
A major challenge in studying these connections is the low rate of connectivity on the one hand (Lefort et al., 2009) and the high diversity of the pyramidal cell population in individual layers (Zhang & Deschênes, 1997, 1998; Larsen et al., 2007). Our own preliminary data demonstrate the feasibility of paired recordings from these synaptic connections, but we need to identify different sub-populations of pyramidal cells based on their axonal projection patterns. Therefore we intend to use fluorescent marker/rabies virus injections (Wickersham et al., 2007) into the different thalamic nuclei in order to retrogradely label cortico-thalamic projecting neurons. For this the pneumatic micro-pump is required. Furthermore, a high-end microscope for electrophysiological recordings from fluorescent neurons in neocortical slices is indispensable. A detailed morphological and ultrastructural (electron microscopic) analysis will reveal whether synaptic contacts at these different connections show specialised morphological characteristics.Furthermore, we plan to investigate how synaptic connections behave under conditions of altered activity. Acetylcholine affects different neocortical neurons differentially by hyperpolarising L4 spiny neurons and depolarising L2/3 and L5 pyramidal cells (Eggermann & Feldmeyer, 2009). We are therefore interested to elucidate its effect in the thalamo-cortico-thalamic feedback loop. We also plan paired synaptic recordings under conditions of - pharmacologically induced - increased network activity (correlates of the in vivo cortical ‘UP’ states) to investigate how synaptic transmission is altered under these conditions. The combination of paired recording, light microscopic, ultrastructural and labelling techniques will allow to reveal whether a connection specificity between layer 4 and subgroups of pyramidal cells in the cortico-thalamic projection layers exists and how the communication between these layers may affect thalamic and neocortical signal processing.