Search

Letter to the Editor

Social isolation poses a severe mental and physiological burden on humans. Most animal models that investigate this effect are based on prolonged isolation, which does not mimic the milder conditions experienced by people in the real world. We show that in adult male rats, acute social isolation causes social memory loss. This memory loss is accompanied by significant changes in the expression of specific mRNAs and proteins in the medial amygdala, a brain structure that is crucial for social memory. These changes particularly involve the neurotrophic signaling and axon guidance pathways that are associated with neuronal network remodeling. Upon regrouping, memory returns, and most molecular changes are reversed within hours. However, the expression of some genes, especially those associated with neurodegenerative diseases remain modified for at least a day longer. These results suggest that acute social isolation and rapid resocialization, as experienced by millions during the COVID-19 pandemic, are sufficient to induce significant changes to neuronal networks, some of which may be pathological.

The basolateral amygdala (BLA), medial prefrontal cortex (mPFC) circuit, plays a crucial role in acquisition and extinction of fear memory. Extinction of aversive memories is mediated, at least in part, by the phosphoinositide-3 kinase (PI3K)/Akt pathway in adult rats. There is recent interest in the neural mechanisms that mediate fear and extinction in juvenile animals and whether these mechanisms are distinctive from those in adult animals. In the present study, we examined (1) changes in phosphorylation of Akt in the BLA and mPFC after fear conditioning and extinction in juvenile and adult rats and (2) the effect of BLA and mPFC localized inhibition of the PI3K following acquisition and extinction of contextual fear memory. Our results show that Akt phosphorylation is increased following acquisition of contextual fear learning in the BLA but not in the mPFC in adult and juvenile rats. Extinction learning was not associated with changes in Akt phosphorylation. Although there were no differences in the pattern of phosphorylation of Akt either in adult or juvenile rats, microinjection of the PI3K inhibitor, LY294002, into the BLA or mPFC elicited differential effects on fear memory acquisition and extinction, depending on the site and timing of the microinjection, as well as on the age of the animal. These results suggest that PI3K/Akt has a differential role in formation, retrieval, and extinction of contextual fear memory in juvenile and adult animals, and point to developmental differences between adult and juvenile rats in mechanisms of extinction.

Learning of a particularly difficult olfactory-discrimination (OD) task results in acquisition of rule learning. This enhancement in learning capability is accompanied by the long-term enhancement of synaptic connectivity between piriform cortex pyramidal neurons. In this study we examined whether olfactory rule learning would modify the predisposition to induce long-term potentiation (LTP) in the pathway projecting from the piriform cortex to the olfactory bulb. We report that OD learning was associated with enhancement in the predisposition to induce LTP. This learning-related effect may be affected by process generation of new granule cells located in the olfactory bulb.

We investigated whether the N-methyl-D-aspartate (NMDA) receptor partial agonist D-cycloserine (DCS, 20 µg/side) microinfused into the basolateral amygdala (BLA) would reverse stress-induced impairment of extinction in two aversive learning paradigms: contextual fear conditioning and conditioned taste aversion (CTA). We found that DCS in the BLA show differential involvement in the extinction of these two paradigms and in its modulation of stress-induced impairment of extinction. This may suggest that the dysfunctional extinction of fear and taste aversion following exposure to a stressful experience may be modulated by different mechanisms.

We investigated MEK and D1 receptors in the ventromedial prefrontal cortex (vmPFC) in consolidation and reconsolidation of recognition memory in rats nonhabituated to the experimental context (NH) or with reduced arousal due to extensive prior habituation (H). The D1 receptor antagonist enhanced consolidation and impaired reconsolidation in NH but impaired consolidation with no effect on reconsolidation in H. The D1 receptor agonist had no effect on consolidation in either H or NH but impaired reconsolidation in both groups. The MEK inhibitor impaired consolidation and reconsolidation, regardless of arousal. Thus, vmPFC D1 receptors and MEK show differential involvement in memory and arousal.

We investigated the role of the ventromedial prefrontal cortex (vmPFC) in extinction of conditioned taste aversion (CTA) by microinfusing a protein synthesis inhibitor or N-methyl-d-asparate (NMDA) receptors antagonist into the vmPFC immediately following a non-reinforced extinction session. We found that the protein synthesis blocker anisomycin, but not the NMDA receptors antagonist D,L-2-amino-5-phosphonovaleric acid, impaired CTA extinction in the vmPFC. Anisomycin microinfusion into vmPFC had no effect on CTA acquisition and by itself did not induce CTA. These findings show the necessary role functional protein synthesis is playing in the vmPFC during the learning of CTA extinction.

The dual impairment of both long-term potentiation (LTP) in the dentate gyrus and spatial memory by N-methyl-D-aspartate (NMDA) blockers such as 2-aminophosphonovaleric acid (APV) or dizocilpine (MK-801) is considered supportive evidence for the hypothesis that LTP-like mechanisms are involved in spatial memory. However, several studies suggest that, at doses that affect aspects of behavior, LTP is not yet blocked. One possible explanation may be that the blockade of NMDA receptors affect processes other than LTP, which are required for learning. In the present study, we assessed in vivo the effects of the NMDA receptor antagonist MK-801 on LTP and on frequency-dependent inhibition, which has previously been shown to reflect activity of GABAergic interneurons in the rat dentate gyrus. We report here that NMDA receptors are instrumental in frequency-dependent inhibition. Furthermore, frequency-dependent inhibition was found to be more sensitive than LTP to the NMDA antagonist MK-801. Our findings indicate that, in addition to the blockade of LTP, the application of NMDA antagonists affects local circuit activity in the dentate gyrus. The results direct attention to the potential role of interneuronal activity in general and of frequency-dependent inhibition in particular in dentate gyrus related behaviors. Hippocampus 1999;9:491–494. © 1999 Wiley-Liss, Inc.

The dual impairment of both long‐term potentiation (LTP) in the dentate gyrus and spatial memory by N‐methyl‐D‐aspartate (NMDA) blockers such as 2‐aminophosphonovaleric acid (APV) or dizocilpine (MK‐801) is considered supportive evidence for the hypothesis that LTP‐like mechanisms are involved in spatial memory. However, several studies suggest that, at doses that affect aspects of behavior, LTP is not yet blocked. One possible explanation may be that the blockade of NMDA receptors affect processes other than LTP, which are required for learning. In the present study, we assessed in vivo the effects of the NMDA receptor antagonist MK‐801 on LTP and on frequency‐dependent inhibition, which has previously been shown to reflect activity of GABAergic interneurons in the rat dentate gyrus. We report here that NMDA receptors are instrumental in frequency‐dependent inhibition. Furthermore, frequency‐dependent inhibition was found to be more sensitive than LTP to the NMDA antagonist MK‐801. Our findings indicate that, in addition to the blockade of LTP, the application of NMDA antagonists affects local circuit activity in the dentate gyrus. The results direct attention to the potential role of interneuronal activity in general and of frequency‐dependent inhibition in particular in dentate gyrus related behaviors. Hippocampus 1999;9:491–494. © 1999 Wiley‐Liss, Inc.

Human neonates are occasionally treated with diuretics, and we investigated whether this causes a long-term enhancement of salt preference. Salt preference was examined in children aged 4–11 years. Twenty one of the children had received furosemide therapy as preterm neonates, and 24 were preterm neonates from the same ward that had no furosemide therapy. No differences were found between the two groups in preferred concentration of NaCl in soup, in consumption of salty items, and in blood and urine sodium and creatinine. However, in a tested subsample, fractional excretion of sodium (FENa) was higher in the neonatally treated children, suggesting increased salt intake. Reported severity of morning sickness in the mother when pregnant with the child, the child's history of diarrhoea and vomiting and degree of dietary salt exposure were obtained by questionnaire. These variables also did not influence salt preference, or blood and urine sodium and creatinine, except for a correlation between dietary salt exposure and blood sodium concentration. We conclude that while the physiological evidence suggests increased salt intake in children treated neonatally with furosemide, more sensitive tests of salt preference at this age are required to reveal any influence early mineralofluid loss may have on salt preference in childhood.