Introduction

I am an Assistant Professor in the Cellular and Cellular and Computational Neuroscience group at the University of Amsterdam (the Netherlands). My recent research focuses on the anatomical and functional network properties of the hippocampus, the parahippocampal region and the amygdala (figure 1). The parahippocampal region is a cortical brain area that is involved in cognitive functions like learning and memory, object recognition, sensory representation and spatial orientation. Two subareas of the parahippocampal region, the perirhinal cortex (PER) and the lateral entorhinal cortex (LEC) form an anatomical link between the neocortex and the hippocampus. Although anatomical connections exist within the PER/EC network (Cappaert et al., 2014), the information transfer through this network occurs with a low probability (Willems et al., 2016) and is hence called the parahippocampal gate. Emotional events, which activate the amygdala - a brain region involved in emotional processing, could modulate this gating process. However, how exactly the gate is modulated is not known. I focus on the anatomical and functional architecture of the hippocampus, parahippocampus and amygdala at 3 levels to unravel the mechanism of the gate (Figure 1).

1. Connectomics

To better understand the network properties, I study the anatomical connectivity of the hippocampus and parahippocampal region, together with Niels van Strien (University of Amsterdam), Prof. Menno Witter (Kavli Institute, Norwegian University of Science and Technology, Trondheim) and Prof Jaap Murre (University of Amsterdam) by developing an interactive connectome of the the hippocampal formation, the parahippocampal region and the retrosplenial cortex (Figure 2, Van Strien et al., 2009; Sugar et al., 2011). A connectome is a comprehensive description of the network elements and connections that form the brain. Such clear and comprehensive knowledge of anatomical connections lies at the basis of understanding network functions. In our current connectome we included almost 2600 anatomical connections of the hippocampal formation, the parahippocampal region and the retrosplenial cortex, which can all be interactively switched on and off. The functional properties of this structural connectome were investigated with a graph analysis (Biniciewicz et al., 2016). In the current project the amygdalar connections are mapped and computational models are developed to investigate the modulatory role of the amygdala onto the hippocampus and the parahippocampal region, during learning and memory.

2. Networks at the population level

The functional organization of the input to the PER/EC network at the population level can be investigated with voltage sensitive dye (VSD) imaging. VSD imaging reveals the population changes in membrane potential in brain tissue, which allows a detailed analysis of the spatial and temporal pattern of network recruitment. For example, we addressed the dynamics of the mouse PER/EC network activity in response to neocortical and amygdalar electrical stimulation by comparing the recruitment sequence (figure 3). When GABA_A dependent inhibition is reduced, both the neocortical and the amygdala activate spatially overlapping regions, although in a distinct spatiotemporal fashion. It is therefore hypothesized that the inhibitory network regulates excitatory activity from both cortical and subcortical areas that has to be transmitted through the PER-LEC network.

3. Networks at the cellular level

To investigate the role of the inhibitory properties and consider the interplay between principal neurons and PV interneurons in processing the synaptic input to the deep layers of the PER-LEC network, we performed double patch clamp experiments. The evoked synaptic input and action potential firing patterns in principal neurons and PV interneurons were recorded to address the functional output of the PER-LEC network once synaptic input is processed in the local circuitry. The excitatory input from the neocortex onto deep layer principal neurons is overruled by strong feedforward inhibition. PV interneurons, with their fast, extensive stimulus-evoked firing, are able to deliver this fast evoked inhibition in principal neurons. This indicates an essential role for PV interneurons in the gating mechanism of the PER-LEC network (Willems et al., 2018).

Selected references

• Willems JGP, Wadman WJ, Cappaert NLM (2018) Parvalbumin interneuron mediated feedforward inhibition controls signal output in the deep layers of the perirhinal-entorhinal cortex. Hippocampus 28(4):281-296. doi: 10.1002/hipo.22830.
• Willems JGP, Wadman WJ , Cappaert NLM (2016) Distinct Spatiotemporal Activation Patterns of the Perirhinal-Entorhinal Network in Response to Cortical and Amygdala Input. Front. Neural Circuits 10:44. doi: 10.3389/fncir.2016.00044
• Binicewicz FZ, van Strien NM, Wadman WJ, van den Heuvel MP, Cappaert NLM (2016). Graph analysis of the anatomical network organization of the hippocampal formation and parahippocampal region in the rat. Brain Struct Funct 221:1607–1621.
• Cappaert NLM, van Strien NM, Witter MP (2015) Hippocampal formation. In G. Paxinos (Ed.) “The rat nervous system” (4th ed.) (pp. 511-573). Amsterdam: Elsevier Academic. DOI: 10.1016/B978-0-12-374245-2.00020-6
• Cappaert NLM, Lopes da Silva FH, Wadman WJ (2009). Spatio-temporal dynamics of theta oscillations in hippocampal-entorhinal slices. Hippocampus 19(11), 1065-1077.
• van Strien NM, Cappaert NLM*, Witter MP (2009). The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network. Nat Rev Neurosci 10(4), 272-82. * Shared first author

Teaching

- Track coordinator or the master "Physiology of Synapses and Networks"

- Member of the teaching committee ‘Psychobioogy’ (BSc)

- Member of the teaching committee 'Biomedical Sciences' (MSc)

- Member of the curriculum team ‘Psychobiology’

- Course coordinator of ‘van Perceptie tot Bewustzijn’, ‘Neurophysiology’ and ‘From synapse to network’

- Lecturer in ‘van Perceptie tot Bewustzijn’, ‘Introductie Pyschobiologie, ‘Neurosystemen’, ‘Neurophysiology’ and other courses

- Senior Teaching Qualification (SKO) & University Teaching Qualification (BKO)