A disinhibition-based model of CA1 place field sequences

Because of the paucity of pattern-generating recurrent excitation in the CA1 hippocampal region, place field sequences are assumed to be inherited from upstream regions. Alternatively, disinhibition may play a role in shaping pyramidal cell activity. We propose a model of CA1 activity using one layer of excitatory cells and one layer of inhibitory cells, with local excitatory- to-inhibitory connectivity, broad inhibitory-to-excitatory connectivity without recurrent excitatory connections, and broad inhibitory-inhibitory connections. The layers need not follow a topographic organization; instead they can represent sequences of place cells structured by local inhibition. Our mathematical model of CA1 neurons with data-inspired connectivity demonstrates place fields sharpened by disinhibition, mimicking a recently discovered decrease in inhibitory input within place fields and matching in vivo patterns of disinhibition. Mathematical analysis of our model suggests the importance of inhibitory-to-excitatory connections in control of place cell firing rate and sparsity. We also demonstrate that a disinhibition-based mechanism of pattern generation is more flexible without recurrent excitation than the recurrent excitation-rich CA3-like model. Finally, we demonstrate disinhibition as an efficient mechanism for internally-generated sequential activity, where the speed of sequential change depends on both input strength and inhibitory-to-excitatory connection strength. Overall, our model suggests that theta time-scale disinhibition is a foundational mechanism of self-organized sequential activity in the CA1 region, and, possibly, in other networks.

The hippocampus is thought to be important for learning and memory. The main output of the hippocampus is through the CA1 region, which contains cells that demonstrate spatially-informative firing patterns. Previous models of place cell activity include recurrent excitatory or increases of inhibitory input within a place field, though it is well known that CA1 exhibits only weak connections between excitatory cells. We provide a population model of CA1 place cell activity without recurrent excitation that replicates many characteristics of place cell activity, such as a decrease in inhibitory input within a place field and increasingly sparse activity with familiarity in the environment. We also demonstrate intrinsic sequential activity through disinhibition. We propose that disinhibition dominates theta-timescale activity in the CA1 region of the hippocampus.