Both Glutamatergic and Gabaergic Neurons are Recruited to be Associative Memory Cells

Abstract

The recruitment of associative memory cells and their working principle for signal storage were studied by in vivo two-photon calcium imaging, AAV-tagged neural tracing, electrophysiology and microRNA analyses. Paired whisker and odor stimulations led to reciprocal cross-modal reflexes, odorant-induced whisker motion and whisker-induced olfaction response. In the mice of expressing cross-modal memory, the piriform and barrel cortices mutually innervated through their axon projections and the new synapses from these axons to target cells. Glutamatergic and GABAergic neurons in the barrel cortex became to encode the newly acquired odor signal alongside innate whisker signal. Piriform cortical neurons encoded the learnt whisker signal alongside innate odor signal. These associative memory neurons were able to distinguish new signal and innate signal as well as to tell their historical association. These associative memory neurons received new synaptic inputs along with native synaptic inputs. In addition, the newly learnt signals were sent to the contralateral cortices through new axons and synapses for unilateral learning toward bilateral memory. The antagomirs of microRNA-324p and microRNA-133a reduced the formation of cross-modal memory, the recruitment of associative memory cells and the formation of new synapses. The co-activations of the sensory cortices initiate their mutual synaptic innervations, which recruit their target cells to be associative memory cells. Our study reveals associative memory cells based on these criteria. They encode associative signals (two or more), receive the synaptic inputs from signals’ origins and send the output signals to control behaviors. The recruitment of associative memory cells is downregulated by changing gene expression, or vice versa. Associative memory cells are recruited in the sensory cortices from our model, compared to fear learning that induces extensive associations between the whole brain excited by electrical shock and the auditory cortex by sound.