Coordinated Plasticity between Barrel Cortical Glutamatergic and GABAergic Neurons during Associative Memory

Abstract

Neural plasticity is associated with memory formation. The coordinated refinement and interaction between cortical glutamatergic and GABAergic neurons remain elusive in associative memory, which we examine in a mouse model of associative learning. In the mice that show odorant-induced whisker motion after pairing whisker and odor stimulations, the barrel cortical glutamatergic and GABAergic neurons are recruited to encode the newly learnt odor signal alongside the innate whisker signal. These glutamatergic neurons are functionally upregulated, and GABAergic neurons are refined in a homeostatic manner. The mutual innervations between these glutamatergic and GABAergic neurons are upregulated. The analyses by high throughput sequencing show that certain microRNAs related to regulating synapses and neurons are involved in this cross-modal reflex. Thus, the coactivation of the sensory cortices through epigenetic processes recruits their glutamatergic and GABAergic neurons to be the associative memory cells as well as drive their coordinated refinements toward the optimal state for the storage of the associated signals.

Associative memory cells: Formation, function and perspective

“…Since inhibiting the function of sensory cortices blocks the reciprocal cross-modal reflex 1, 3, 15 , the primary area for associative memory is likely located in sensory cortices, where mutual synapse innervations and associative memory cells are recruited after associative learning 1, 3, 7 .…”

“…The neurons that encode either one of signals are called new memory cells or innate memory cells. Associative memory cells include glutamatergic neurons, GABAergic neurons and astrocytes 1, 3, 7 . miRNA-mediated epigenetic processes also appear to be involved 7, 15 .…”

“…Associative memory cells include glutamatergic neurons, GABAergic neurons and astrocytes 1, 3, 7 . miRNA-mediated epigenetic processes also appear to be involved 7, 15 . Associative memory cells and mutual synapse innervations among sensory cortices constitute the cellular substrates for memory to specific associated signals.…”

“…The number, activity level and plasticity of associative memory cells, as well as the connection and activity strengths in their input and output partners, set up the power and persistence of information storage and memory presentation. With associative memory cells in the sensory cortices 1, 3, 7, 16 , their axon-innervated downstream brain cells are able to encode these associated signals 17– 20 . The stimulations to any of these areas in the neural circuits from sensory cortices to behavior- and emotion-controlled brain nuclei can induce memory presentation 21– 27 .…”

“…In fact, such signals can be retrieved reciprocally, i.e., one signal induces the recall of its associated signals, or the other way around. The mutual synapse innervations among the co-activated sensory cortices and the associative memory cells in these areas are presumably recruited during associative learning 1, 3, 5– 7 .…”