Differential Effects of Inactivation of Discrete Regions of Medial Prefrontal Cortex on Memory Consolidation of Moderate and Intense Inhibitory Avoidance Training.

María E Torres-García,Gina L Quirarte,Andrea C Medina,Roberto A Prado-Alcalá

doi:10.3389/fphar.2017.00842

María E Torres-García, Gina L Quirarte + Show 2 more

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https://doi.org/10.3389/fphar.2017.00842

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Abstract

It has been found that the medial prefrontal cortex (mPFC) is involved in memory encoding of aversive events, such as inhibitory avoidance (IA) training. Dissociable roles have been described for different mPFC subregions regarding various memory processes, wherein the anterior cingulate cortex (ACC), prelimbic cortex (PL), and infralimbic cortex (IL) are involved in acquisition, retrieval, and extinction of aversive events, respectively. On the other hand, it has been demonstrated that intense training impedes the effects on memory of treatments that typically interfere with memory consolidation. The aim of this work was to determine if there are differential effects on memory induced by reversible inactivation of neural activity of ACC, PL, or IL produced by tetrodotoxin (TTX) in rats trained in IA using moderate (1.0 mA) and intense (3.0 mA) foot-shocks. We found that inactivation of ACC has no effects on memory consolidation, regardless of intensity of training. PL inactivation impairs memory consolidation in the 1.0 mA group, while no effect on consolidation was produced in the 3.0 mA group. In the case of IL, a remarkable amnestic effect in LTM was observed in both training conditions. However, state-dependency can explain the amnestic effect of TTX found in the 3.0 mA IL group. In order to circumvent this effect, TTX was injected into IL immediately after training (thus avoiding state-dependency). The behavioral results are equivalent to those found after PL inactivation. Therefore, these findings provide evidence that PL and IL, but not ACC, mediate LTM of IA only in moderate training.

Highlights

A large body of research has shown that interference with neural activity shortly after a learning experience results in a significant deficiency of memory consolidation (McGaugh, 1966, 2000; Lechner et al, 1999; Izquierdo and McGaugh, 2000), lending strong support to the consolidation hypothesis put forward by Müller and Pilzecker (1900)
The retention deficit observed in the present study gives support to the findings of Santos-Anderson and Routtenberg (1976) and of Jinks and McGregor (1997). The former authors showed that low-level electrical stimulation of the ventral aspect of the medial prefrontal cortex (mPFC) interfered with memory consolidation of inhibitory avoidance (IA), and the latter found that electrolytic lesions of prelimbic cortex (PL) produced a deficit in IA. These findings indicate that PL has similar functions to those of the striatum, hippocampus, amygdala, and substantia nigra regarding memory consolidation of IA, i.e., these structures are necessary for memory consolidation under conditions of moderate training because interference with neural activity of any one of them impedes the formation of long-term memory
The data obtained in this experimental series indicate that (a) memory consolidation of IA is not dependent on neural activity of the anterior cingulate cortex (ACC); (b) normal activity of PL is essential for memory consolidation of moderate IA training, but not for acquisition or for consolidation of intense training; (c) normal activity of infralimbic cortex (IL) is essential for memory consolidation of moderate IA training but not for acquisition or for consolidation of intense training

Summary

Introduction

A large body of research has shown that interference with neural activity shortly after a learning experience results in a significant deficiency of memory consolidation (McGaugh, 1966, 2000; Lechner et al, 1999; Izquierdo and McGaugh, 2000), lending strong support to the consolidation hypothesis put forward by Müller and Pilzecker (1900) This hypothesis implies that memory fixation requires time (consolidation) and that memory is vulnerable during the period of consolidation. When learning is brought about through intense training, memory formation is guarded against a host of amnestic treatments (For a review see Prado-Alcalá et al, 2012).1 This protective effect has been consistently found after training of instrumental tasks, where a reinforcer is available after performance of a specific response (Prado-Alcalá and Cobos-Zapiaín, 1977, 1979; Prado-Alcalá et al, 1980). Electrolytic lesions of lateral and basal nuclei of the amygdala impaired acquisition of a Sidman avoidance task but enhanced training protected performance of this task (LazaroMuñoz et al, 2010)

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