β-adrenergic receptors modulate CA1 population coding during cumulative spatial memory formation and updating

Hippocampal neuronal ensembles are likely to support the acquisition, stabilization and updating of spatial experience. Spatial learning is typically cumulative, but little is known about how neuronal ensembles are manifested during this process. Here, we used wide-field Ca 2+ -imaging to monitor CA1 pyramidal cells during cumulative item-place learning in adult male CBA/CaOlaHsd mice. In control mice, initial learning prompted activity in a population of CA1 neurons, some of which re-appeared during re-exposure to the same item-place configuration 60 min after 1 st exposure. Item-place reconfiguration (60 min later) caused a change in population dynamics as reflected by alterations in neuronal recruitment and reactivation patterns. Place cell-like properties, population burst activity, and functional connectivity were consistent with the encoding and updating of item-place memory. To examine the role of noradrenergic neuromodulation on these processes, we pharmacologically antagonized β-adrenergic receptors(β-AR) prior to the 1 st item-place exposure. This led to reduced cellular recruitment, disrupted ensemble reactivation, reduced spatial tuning, dampened population bursts, and altered functional connectivity within neurons. This was accompanied by impaired spatial learning compared to controls. Our results reveal the population activity of CA1 neurons during item-place learning and show that β-AR support memory function by influencing both neuronal and network-level dynamics.