JClub: Preexisting hippocampal network dynamics constrain optogenetically induced place fields

How neural networks reorganise in response to external stimulation? Is place cell selectivity caused by selective excitatory inputs or local network activity?

McKenzie et al. (Neuron, 2021), studied these questione in the hippocampal CA1 region in mice during navigation on a linear track. Typical CA1 excitatory neurons show strong spatial selectivity (place fields). As there are no recurrent connections between CA1 pyramidal cells, the spatial tuning of these neurons is thought to be a consequence of their tuned inputs from CA3 and entorhinal cortex. Confirming this view, previous studies demonstrated that new place field can be produced by strong intracellular depolarisation of CA1 pyramidal neurons resulting in large dendritic plateau potentials and burst firing via long lasting plasticity of the feed forward inputs.

Here the authors combined extracellular recordings from many CA1 neurons with the optogenetic activation of a subpopulation of the excitatory cells. 2-10 repetition of the optogenetic stimulation during running resulted in a long lasting change in the selectivity of both the stimulated and the non-stimulated neurons, with the resulting selectivity being independent of the location of the stimulation. Moreover, for the majority of the neurons, the location of the new place field could be predicted from the activity (firing rate or only the percentage of spikes in a burst) of the cells before the stimulation period.

Can we explain these results by the standard Hebbian synaptic plasticity between the inputs and the output? This would predict that inputs active in the stimulation zone are most affected and thus stimulated neurons should develop or loose place cells typically around the stimulation zone with other locations much less affected. An alternative mechanism, proposed by the authors, is that reorganisation of the local inhibitory feed-back circuit may be responsible for the changes. If this is true, that also means that indirect recurrent connectivity (i.e., lateral inhibition) between CA1 pyramidal neurons has a much stronger role in shaping spatial selectivity of these cells than we previously thought.