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, AAVtagged 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.

Associations of Unilateral Whisker and Olfactory Signals Induce Synapse Formation and Memory Cell Recruitment in Bilateral Barrel Cortices: Cellular Mechanism for Unilateral Training Toward Bilateral Memory

“…Their coordinated changes drive the barrel cortex to the optimal excitatory state, which facilitates the recruitment of the cortical neurons to be associative memory cells that encode the newly acquired odor signal and the innate whisker signal (Figure 3). Therefore, the co-activations of barrel and piriform cortices may lead to their mutual innervations (Wang et al, 2014, 2016). The axon and synapse innervations from the piriform cortex onto barrel cortical neurons dive them to be recruited as associative memory cells, and in turn the axons of these associative memory neurons in this pair-trained barrel cortex project toward its CBC to form new synapses for the recruitment and refinement of contralateral neurons, leading to unilateral training toward bilateral memory (Figure 9).…”

“…In this regard, the associative activation of the piriform and barrel cortices is the primary driving force for unilateral training toward bilateral memory. Molecular mechanism for these processes on both sides remains to be studied, in which microRNA-324 and microRNA-133a appear involved (Wang et al, 2016). …”

“…Their axons project toward motor-related cortices to initiate memory presentation. Their recruitment is regulated by the genes and proteins related to associative memory (Wang et al, 2016). The working principle of these associative memory cells may be based on the facilitation of their excitatory states driven by the newly innervated synapses from other sensory cortices.…”

“…In this regard, the somatosensory cortex, which may be involved in information storage (Diamond et al, 2003; Diamond and Arabzadeh, 2013), would be ideally used to study the recruitment of bilateral connections for unilateral learning toward bilateral memory, instead of the studies by using special sensory cortices in that splitting hemispheres is needed. After associative memory is onset in sensory cortices (Weinberger, 2004, 2007; Letzkus et al, 2012; Wang et al, 2015), the nerve cells in the trained somatosensory cortices can be recruited as associative memory cells (Wang et al, 2014, 2015, 2016). These associative memory cells hypothetically send the newly learnt sensory signal to the neurons in the contralateral somatosensory cortex by their axon projections and new synapse innervations, such that the neurons in the contralateral cortex are recruited as associative memory cells for unilateral training toward bilateral memory.…”

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

“…In this cross-modal reflex, the retrieval of the unconditioned signals is induced by the conditioned signals, and the brain areas that encode the unconditioned signals may become processing the conditioned signals. Current reports indicate that paired-stimulations to mouse whiskers and olfaction lead to odorant-induced whisker motion and that the barrel cortical neurons become encoding odor signal alongside whisker signal [28, 29, 37, 38]. As the barrel cortex naturally encodes whisker signal, that is, odor signal is new to the barrel cortex before associative learning, this model should be useful to investigate cellular and molecular mechanisms underlying the storage and retrieval of the newly learnt information.…”