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A Translaminar Cortical Circuit Driven by Higher Order Thalamus Initiates Learning-Related Synaptic Plasticity

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posted on 01.08.2018, 00:00 authored by Nicholas AudetteNicholas Audette
The cortical column is an evolutionarily conserved and expanded processing unit that underlies mammalian perception, learning, and memory. A unifying trait of the cortical column across these functions is its capacity to undergo experience-dependent plasticity, and decades of research has used the somatosensory cortex as a model circuit to link this plasticity to specific cortical circuits. Patterns of local connectivity and primary thalamic input generated a model of sequential processing where computations are performed as information proceeds serially across cortical layers, with learning-dependent changes occurring at intracortical connections. While this model fits many features of the cortical circuit, a growing body of work suggests that the higher order posterior medial thalamic nucleus (POm) is also well-positioned to influence activity across multiple layers of the cortical column.
We set out to investigate the potential contribution of POm to cortical activity patterns under basal conditions and during sensory learning by measuring electrophysiological responses of cortical neurons following optogenetic activation of thalamic axons in vitro. We first used targeted whole-cell patch clamp recording in combination with transgenic mouse lines to determine the cell-type specific functional connectivity of POm afferents in control animals. In deep layers, POm provides strong, direct input to excitatory neurons synchronized by fast, feedforward inhibition from parvalbumin-expressing neurons. Alternatively, POm provides weaker direct input to excitatory neurons in superficial layers, but can facilitate over the course of stimulation due to weaker, delayed feedforward inhibition from 5HT3a neurons. In both layers, tonically active somatostatin-expressing inhibitory neurons were silenced by 5HT3a neurons.
To determine if this thalamocortical circuit is a locus of synaptic changes during learning, we developed a high throughput home-cage sensory association training assay that paired a multi-whisker stimulus with a water reward. We discovered that POm activation drove dramatically increased cortical activity in both deep and superficial layers after just 24 hours of training, when behavioral evidence for a learned association first emerged. This increase in activity did not occur in primary thalamocortical pathways and was caused by a learning-specific increase in synaptic strength at the POm to layer 5 synapse. Over longer durations of training, synaptic plasticity occurred at both thalamocortical (POm) and intracortical (layer 2) inputs onto layer 2 excitatory neurons. Together, our results show that the higher order thalamic nucleus POm drives characteristic patterns of activity in multiple cortical layers and is the initiator of cortical columnar rearrangements during sensory learning. This study provides a much-needed update to the long-held sequential view of cortical processing.




Degree Type



Biological Sciences

Degree Name

  • Doctor of Philosophy (PhD)


Alison Barth

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