A mouse model of autoimmune encephalitis

Abstract

This scientific commentary refers to ‘Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice’ by Planagumà et al. (doi: 10.1093/brain/awu310).

Figure 1

NMDAR-Abs impair cognition in mice. Left: A mouse exposed to a novel object will spend time exploring it. In the presence of two novel objects, the animal will spend an equal amount of time exploring each (top left: habituation). However, a mouse exposed to a previously encountered object and a novel one will spend more time exploring the novel object. The mouse will then have a high novel object recognition (NOR) index (the ratio of time spent exploring the novel object : time spent exploring both objects) (bottom left: high NOR index). The extent to which the mouse prefers the novel object is assumed to reflect the strength of its memory for the previously encountered object. At the cellular level (magnified synapse), this behaviour is thought to reflect long-term potentiation, a form of synaptic plasticity. Long-term potentiation relies on the activation of NMDA receptors and on intracellular signalling that leads to an increased surface expression of AMPA receptors at the synapse. Right: In the experiments of Planagumà et al., mice infused with NMDAR-Abs show normal exploratory behaviour when presented with two novel objects (top right: habituation). However, when exposed to a previously encountered object and a novel one, the mice again spend the same amount of time exploring each of the two objects, indicating an impairment in memory. The animals thus have a low NOR index (bottom right: low NOR index). Although Planagumà et al. demonstrated a clear effect of NMDAR-Abs on cognition in vivo, the mechanisms by which these autoantibodies act at the synaptic level remain to be deciphered. In particular, efforts are required to identify the cellular and subcellular location of the NMDARs targeted, and the synaptic modifications leading to the alteration of long-term potentiation.