Src and Memory: A Study of Filial Imprinting and Predispositions in the Domestic Chick

Maia Meparishvili,Lela Chitadze,Revaz Solomonia,Vincenzo Lagani,Brian Mccabe

doi:10.3389/fphys.2021.736999

Maia Meparishvili, Lela Chitadze + Show 3 more

Open Access

https://doi.org/10.3389/fphys.2021.736999

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Abstract

Visual imprinting is a learning process whereby young animals come to prefer a visual stimulus after exposure to it (training). The available evidence indicates that the intermediate medial mesopallium (IMM) in the domestic chick forebrain is a site of memory formation during visual imprinting. We have studied the role of Src, an important non-receptor tyrosine kinase, in memory formation. Amounts of total Src (Total-Src) and its two phosphorylated forms, tyrosine-416 (activated, 416P-Src) and tyrosine-527 (inhibited, 527P-Src), were measured 1 and 24 h after training in the IMM and in a control brain region, the posterior pole of nidopallium (PPN). One hour after training, in the left IMM, we observed a positive correlation between the amount of 527P-Src and learning strength that was attributable to learning, and there was also a positive correlation between 416P-Src and learning strength that was attributable to a predisposition to learn readily. Twenty-four hours after training, the amount of Total-Src increased with learning strength in both the left and right IMM, and amount of 527P-Src increased with learning strength only in the left IMM; both correlations were attributable to learning. A further, negative, correlation between learning strength and 416P-Src/Total-Src in the left IMM reflected a predisposition to learn. No learning-related changes were found in the PPN control region. We suggest that there are two pools of Src; one of them in an active state and reflecting a predisposition to learn, and the second one in an inhibited condition, which increases as a result of learning. These two pools may represent two or more signaling pathways, namely, one pathway downstream of Src activated by tyrosine-416 phosphorylation and another upstream of Src, keeping the enzyme in an inactivated state via phosphorylation of tyrosine-527.

Highlights

Src is a non-receptor protein tyrosine kinase that participates in a number of neuronal processes including neurotransmitter release, neurotransmitter receptor function, and synaptic plasticity
One Hour After the End of Training A significant positive correlation was found for 416P-Src (Figure 2A), but the residual variance from the regression was significantly lower than the variance in untrained chicks (Table 1), implicating 416P-Src at this time after training in a predisposition reflects the readiness of chicks to learn
There was no significant correlation for Total-Src, and the ratio 527P-Src/Total-Src behaved to 527P-Src alone, with the exception that the level of this ratio at maximum preference score was significantly greater than the mean for untrained chicks only at the P < 0.1 level (Table 1)

Summary

Introduction

Src is a non-receptor protein tyrosine kinase that participates in a number of neuronal processes including neurotransmitter release, neurotransmitter receptor function, and synaptic plasticity. Autophosphorylation of tyrosine-416 in the activation loop of Src is thought to increase Src activity, whereas phosphorylation at tyrosine-527 by other kinases suppresses Src activity (Ohnishi et al, 2011). There is evidence that Src participates in learning and/or memory, possibly via phosphorylation of N-methyl-D-aspartate receptors, but its role is poorly understood. Overexpression of Src affects excitatory synaptic transmission in area CA3 of the mammalian hippocampus, and impairs fear memory (Yan et al, 2017). Upregulation of Src mRNA was observed in area CA3 (Zhao et al, 2000). Increased autophosphorylation of Src enhances hippocampal long-term potentiation and spatial memory (Wang et al, 2018). To clarify the role of Src in memory, it would be helpful to simultaneously measure its activated form phosphorylated at tyrosine-416 (416P-Src) and its inactive form phosphorylated at tyrosine-527 (527P-Src) in a vertebrate brain region where memory is encoded, and for a type of learning for which a graded measurement of memory strength is available

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