Nature Neuroscience 20 January Two new papers
Two new papers, published back to back by Nature Neuroscience on January 20, suggest that the entorhinal grid map may emerge from an inhibitory network in layer II of medial entorhinal cortex. The first paper shows that grid cells are connected exclusively by way of inhibitory interneurons. The second paper shows that in order to produce grid patterns, this network requires excitatory drive from the hippocampus.
The papers are a collaborative effort of several research groups at the Kavli Institute. Experimental data, obtained by Jay Couey in the Witter group and Tora Bonnevie and colleagues in the Moser group, formed the basis for a computational model of how the brain generates grid cells. The modeling was performed by Aree Wittoelar and Benjamin Dunn in the Roudi group.
It is commonly thought that grid cells are necessary for the formation of place cells, but the reverse may also be the case. The two studies show that the medial entorhinal cortex has a network present in layer II which is sufficient to generate grid cells on the condition that a constant excitatory drive is present. Bonnevie et al show that this excitatory drive may come from the hippocampus Couey et al show that layer II stellate cells of the medial entorhinal cortex are embedded within an exclusively recurrent inhibitory network. Using clustered whole-cell in vitro slice recordings of neurons in MEC layer II, Couey et al.found no evidence of direct stellate cell to stellate cell excitatory connectivity in MEC layer II in adult tissue slices. In contrast, stellate cells were highly connected with fast-spiking interneurons. Precisely timed presynaptic activity in small groups of stellate cells were able to activate the local inhibitory microcircuitry with high fidelity in a frequency-independent manner.
A simplified uniform inhibitory attractor model was shown to be sufficient to generate grid-cell activity. The experimental data suggest an exclusively inhibitory network with a bimodal distribution, in which connections are either absent or have stable amplitudes. The simulations showed that in a network in which principal cells are coupled exclusively through all-or-none inhibi-tory interneurons, such as among stellate cells in layer II of the medial entorhinal cortex, grid cells can only be formed in the presence of steady external excitation. Bonnevie et al. provide evidence that such excitatory input may originate from the hippocampus. Steady excitatory input from the hippocampus was found to be necessary for the expression of grid patterns. Inactivation of the hippocampus selectively extinguished grid activity, and cells became head direction modulated instead. Taken together, the experimental data and network simulations suggest that in the absence of excitatory hip¬pocampal feedback, the recurrent interactions between grid cells break down, and external inputs from other areas obtain stronger control of the discharge pattern of the individual grid cells. One function of excitatory projections from the hippocampus, and other structures, may thus be to control the influence of the intrinsic network properties as compared to the input from neighboring regions in determining the firing pattern of the stellate-cell network
