Sensory-evoked LTP driven by dendritic plateau potentials in vivo

Abstract

Long-term synaptic potentiation (LTP) is thought to be a key process in cortical synaptic network plasticity and memory formation. Hebbian forms of LTP depend on strong postsynaptic depolarization, which in many models is generated by action potentials that propagate back from the soma into dendrites. However, local dendritic depolarization has been shown to mediate these forms of LTP as well. As pyramidal cells in supragranular layers of the somatosensory cortex spike infrequently, it is unclear which of the two mechanisms prevails for those cells in vivo. Using whole-cell recordings in the mouse somatosensory cortex in vivo, we demonstrate that rhythmic sensory whisker stimulation efficiently induces synaptic LTP in layer 2/3 (L2/3) pyramidal cells in the absence of somatic spikes. The induction of LTP depended on the occurrence of NMDAR (N-methyl-d-aspartate receptor)-mediated long-lasting depolarizations, which bear similarities to dendritic plateau potentials. In addition, we show that whisker stimuli recruit synaptic networks that originate from the posteromedial complex of the thalamus (POm). Photostimulation of channelrhodopsin-2 expressing POm neurons generated NMDAR-mediated plateau potentials, whereas the inhibition of POm activity during rhythmic whisker stimulation suppressed the generation of those potentials and prevented whisker-evoked LTP. Taken together, our data provide evidence for sensory-driven synaptic LTP in vivo, in the absence of somatic spiking. Instead, LTP is mediated by plateau potentials that are generated through the cooperative activity of lemniscal and paralemniscal synaptic circuitry.

Gating of hippocampal activity, plasticity, and memory by entorhinal cortex long-range inhibition

“…Given that dendritic spikes are normally suppressed by strong feedforward inhibition(9), the ability of the LRIPs to enhance dendritic spiking during a precise temporal window may contribute to the dendritic spike firing in vivo observed during behaviorally relevant cooperative activity(39). The LRIP-dependent dendritic spikes are likely to participate in the induction of ITDP and the fine-tuning of learning and memory, based on the role of such spikes in both other forms of Ca 2+ -dependent synaptic plasticity(35, 36, 40) and non-linear gain modulation during associative learning(35) and sensory tuning(41). …”

Pathway-specific reorganization of projection neurons in somatosensory cortex during learning

“…The increased sensitivity to touch in M1P neurons persisted post-training and could be a result of a strengthening or disinhibition of feedforward responses in S1 (refs. [25][26][27][28][29]. During this period the session-to-session response variability of M1P neurons was reduced compared to baseline conditions, suggesting that sensory representation in these neurons was stabilized.…”

Spontaneous Activity Drives Local Synaptic Plasticity In Vivo

“…This fine-scale organization of synaptic inputs had been previously predicted by theoretical studies proposing that synaptic clustering can boost the computational power of a neuron, because it would allow parallel information processing by supra-linear integration of synchronized synaptic inputs in individual dendritic units (Poirazi and Mel, 2001). Since these early predictions, it has been found that supra-linear integration is required for high-level sensory processing (Lavzin et al, 2012;Palmer et al, 2014;Smith et al, 2013) and synaptic plasticity in vivo (Cichon and Gan, 2015;Gambino et al, 2014). Therefore, the clustering of co-active inputs by spontaneous activity could provide the basis for future sensory processing by enabling supra-linear integration.…”