Dendritic Integration of Synaptic Signals in Memory Generation

• Applicant: Tobias Bock, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 570207552

Every second of our lives, we are bombarded by a multitude of sensory information. Visual, auditory, tactile and olfactory stimuli need to be organized and prioritized and our attention needs to be focused on the most important - or salient - information that allows us to perform tasks productively. A similar filter needs to be applied to the mechanisms by which we generate memory. As we lack the capacity to memorize every moment we experience, salient information is prioritized. Understanding of this filtering mechanism is crucial for the understanding of memory generation and may play an important role in neurodegenerative diseases, affecting memory, such as Alzheimer’s disease and other forms of dementia. But how is information filtered and salience determined within the brain? The long apical dendrites of pyramidal neurons (PNs) have been implicated in the filtering for salient information as they span wide areas in both the cortex and the hippocampus and integrate sensory signals with inputs from higher order brain regions. Recently, we discovered a new mechanism by which small changes in the membrane potential at the cell body (soma) of PNs in the CA1 region of the hippocampus can modulate the impact of distal dendritic signals, which carry sensory information1. Our data suggests that coincident synaptic input at the soma from higher order brain regions, such as area CA2 of the hippocampus and sensory input at the dendrites will increase both the firing of action potentials and synaptic plasticity in these cells. As the activity of these neurons has been shown to mediate spatial and sequential memory, we hypothesize that driving synaptic input specifically to the soma of these neurons can affect memory generation. Based on this background we propose to investigate how synaptic circuits that drive inputs to the somatic region of hippocampal PNs affect memory generation and if this input can provide a filter for salient information. Specifically, we are structuring the study in 2 aims: 1. We plan to investigate the impact of multiple synaptic inputs to CA1 PNs on the integration of dendritic input and its effect on synaptic plasticity. To achieve this, we will obtain intracellular recordings from the CA1 PNs in acute brain slices of mice, expressing the opsin ChrimsonR in area CA2, which allows optogenetic stimulation. 2. We will investigate the impact of synaptic inputs on memory generation by recording the emergence and remapping of place fields in a population of CA1 PNs, using in vivo 2-photon imaging, while stimulating CA2 inputs.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Björn Michael Kampa