Learning-related plasticity of dendritic inhibition in neocortical layer 1
Abstract: Transient breaks in the excitation-inhibition ratio termed disinhibition have been shown to contribute to both memory acquisition and expression in a number of recent studies. However, whether disinhibition occurs throughout the somatodendritic domain of pyramidal neurons, or alternatively represents a redistribution of inhibition within the neuron remains little understood. To address this question, here we focus on neocortical layer 1, a key location for processing of top-down information implicated in learning. Using a novel genetic marker for a subpopulation of layer 1 interneurons (Ndnf) in combination with in vivo 2-photon calcium imaging, in vitro electrophysiology, viral tracing and optogenetics, we find that Ndnf positive layer 1 interneurons in auditory cortex provide inhibition widely to interneurons in layer 1 and lower layers, as well as the distal dendrites of pyramidal neurons. These connections recruit a strong component of GabaB receptor signalling, and thereby control the initiation of dendritic spikes in pyramidal cells. To address whether Ndnf positive layer 1 interneurons show learning-related plasticity, we combined in vivo calcium imaging with a form of cortex-dependent auditory fear learning. These experiments reveal that sensory responses of Ndnf positive layer 1 interneurons are potentiated in response to learning in proportionality to the strength of the memory. In contrast, a second source of dendritic inhibition derived from somatostatin-positive Martinotti cells remains unchanged after learning. Together, these results indicate that, in addition to disinhibition, memory retrieval is associated with an increase in a specialized from of dendritic inhibition.