Associative Memory Extinction Is Accompanied by Decayed Plasticity at Motor Cortical Neurons and Persistent Plasticity at Sensory Cortical Neurons

Abstract

Associative memory is essential for cognition, in which associative memory cells and their plasticity presumably play important roles. The mechanism underlying associative memory extinction vs. maintenance remains unclear, which we have studied in a mouse model of cross-modal associative learning. Paired whisker and olfaction stimulations lead to a full establishment of odorant-induced whisker motion in training day 10, which almost disappears if paired stimulations are not given in a week, and then recovers after paired stimulation for an additional day. In mice that show associative memory, extinction and recovery, we have analyzed the dynamical plasticity of glutamatergic neurons in layers II–III of the barrel cortex and layers IV–V of the motor cortex. Compared with control mice, the rate of evoked spikes as well as the amplitude and frequency of excitatory postsynaptic currents increase, whereas the amplitude and frequency of inhibitory postsynaptic currents (IPSC) decrease at training day 10 in associative memory mice. Without paired training for a week, these plastic changes are persistent in the barrel cortex and decayed in the motor cortex. If paired training is given for an additional day to revoke associative memory, neuronal plasticity recovers in the motor cortex. Our study indicates persistent neuronal plasticity in the barrel cortex for cross-modal memory maintenance as well as the dynamical change of neuronal plasticity in the motor cortex for memory retrieval and extinction. In other words, the sensory cortices are essential for long-term memory while the behavior-related cortices with the inability of memory retrieval are correlated to memory extinction.

Synapse Innervation and Associative Memory Cell Are Recruited for Integrative Storage of Whisker and Odor Signals in the Barrel Cortex through miRNA-Mediated Processes

“…The two groups of mice in postnatal day 20 were treated by microinjecting the antagomirs of miRNA-324-5p/miRNA-133a-3p and the control of these antagomirs into barrel cortices, respectively. Forty-eight hours after the injection, these mice were trained by pairing mechanic whisker stimulus (WS) with odor stimulus (OS, butyl acetate toward their noses; Wang et al, 2015 ; Gao et al, 2016 ; Yan et al, 2016 ; Guo et al, 2017 ; Liu et al, 2017 ; Zhao et al, 2017 ). The concentration of butyl acetate was 99.99% in analytic purity.…”

“…In entire experimental procedures, these mice were not experiencing stressful condition and circadian disturbance. In addition, the mice have normal whisking and symmetric whiskers (Wang et al, 2015 ; Gao et al, 2016 ; Yan et al, 2016 ; Guo et al, 2017 ).…”

“…Whisking frequency and whisker retraction time were significantly increased as well as the latency of whisker motion in response to odor-test was significantly reduced, compared with control and before the training. As this type of whisker motion induced by odorant was originally induced by WS, the odor signal evoked a recall of whisker signal and led to whisker motion (Wang et al, 2015 ; Gao et al, 2016 ; Yan et al, 2016 ; Guo et al, 2017 ).…”

Activity strengths of cortical glutamatergic and GABAergic neurons are correlated with transgenerational inheritance of learning ability

“…In terms of information retrievals, associative memory cells and their upregulations boost their ability to activate the neurons in the downstream brain areas for behavioral reactions and memory presentations. If the sensitivity and intrinsic property of these associative memory cells are increased, their driving to downstream neurons may lead to the elevated activity in brain areas related to behavior and emotion reactions for memory presentation, otherwise, memory extinction [ 1 , 23 ]. If associative memory cells are over-excited, their pathological associations may be related to evoke illusion, delusion and convulsion [ 17 ].…”

“…As cortical glutamatergic and GABAergic neurons are recruited as associative memory cells for the storage of associated signals [ 22 , 29 – 31 ], how these recruited glutamatergic and GABAergic neurons are refined for associative memory including transgenerational process remains unclear [ 17 , 32 ]. Current reports show the upregulation of cortical glutamatergic neurons and the downregulation of GABAergic neurons during associative memory [ 17 , 23 ]. Whether the coordinated plasticity among these neurons is correlated to the transgenerational inheritance of associative learning needs to be examined.…”