Learning-Related Plasticity in Dendrite-Targeting Layer 1 Interneurons

Abstract

SummaryA wealth of data has elucidated the mechanisms by which sensory inputs are encoded in the neocortex, but how these processes are regulated by the behavioral relevance of sensory information is less understood. Here, we focus on neocortical layer 1 (L1), a key location for processing of such top-down information. Using Neuron-Derived Neurotrophic Factor (NDNF) as a selective marker of L1 interneurons (INs) and in vivo 2-photon calcium imaging, electrophysiology, viral tracing, optogenetics, and associative memory, we find that L1 NDNF-INs mediate a prolonged form of inhibition in distal pyramidal neuron dendrites that correlates with the strength of the memory trace. Conversely, inhibition from Martinotti cells remains unchanged after conditioning but in turn tightly controls sensory responses in NDNF-INs. These results define a genetically addressable form of dendritic inhibition that is highly experience dependent and indicate that in addition to disinhibition, salient stimuli are encoded at elevated levels of distal dendritic inhibition.Video Abstract

Nonlinear relationship between multimodal adrenergic responses and local dendritic activity in primary sensory cortices

“…225mice, we measured the change in pupil diameter in response to the auditory cues (CSversus CS + ) during habituation and recall(Abs et al 2018;Garcia-Junco-Clemente et al 2019, …”

“…Notably, under freely behaving conditions, the mice showed a prominent and discriminative fear response to the CS+ ( Figure 3B, CSfreezing: 20.86% ± 2.97%, CS + freezing: 71.75 ± 5.11%, n = 21 mice; p < 0.001, paired t test), indicating successful fear memory learning. To estimate fear expression in head-fixed mice, we measured the change in pupil diameter in response to the auditory cues (CSversus CS + ) during habituation and recall (Abs et al 2018; Garcia-Junco-Clemente et al 2019, Figure 3C). Following fear conditioning, the pupil evoked responses 230 increased for the CS + but not for the CS -( Figure 3D-F; CSbefore: 0.46% ± 1.46%, CS + before: -0.57% ± 0.62%; n = 7 mice, 263 trials; p = 0.47, paired t test; CSafter: 1.88% ± 0.45%, CS + after: 10.2% ± 2.15%, n = 9 mice, 352 trials; p < 0.01 paired t test).…”

Dendritic GABAB receptors control nonlinear information transfer along the dendro-somatic axis in layer 5 pyramidal neurons

“…NGFCs receive inputs from many afferent cortical and subcortical areas that project to L1 of the cortex (Abs et al, 2018). In general, these inputs signal top-down information from higher order brain areas that control the processing of bottom-up information that is locally processed in the specific cortical area (Larkum, 2013).…”

“…Interestingly, NGFCs also engage a particularly slow form of ionotropic inhibition that reflects the slow GABA dynamics within the synaptic cleft as well as the slow receptor kinetics of highaffinity GABAAR in the postsynaptic membrane (Tamas et al, 2003;Karayannis et al, 2010;Schulz et al, 2018). A recent study demonstrated that a large fraction of L1 interneurons that express Neuron-Derived Neurotrophic Factor (NDNF) inhibits postsynaptic pyramidal neurons by a combination of slow GABAAR and GABABRmediated IPSCs as it is typical for NGFCs (Abs et al, 2018). Furthermore, NDNF+ interneurons effectively inhibited Ca 2+ spikes evoked in the apical dendrite of L5 pyramidal neurons (Abs et al, 2018).…”

“…A recent study demonstrated that a large fraction of L1 interneurons that express Neuron-Derived Neurotrophic Factor (NDNF) inhibits postsynaptic pyramidal neurons by a combination of slow GABAAR and GABABRmediated IPSCs as it is typical for NGFCs (Abs et al, 2018). Furthermore, NDNF+ interneurons effectively inhibited Ca 2+ spikes evoked in the apical dendrite of L5 pyramidal neurons (Abs et al, 2018). Therefore, NDNF+ interneurons and other NGFCs in the superficial cortical layers are the prime candidates to activate dendritic GABABRs in L5 pyramidal neurons.…”