Bidirectional switch of the valence associated with a hippocampal contextual memory engram

The valence of memories is malleable because of their intrinsic reconstructive property. This property of memory has been used clinically to treat maladaptive behaviours. However, the neuronal mechanisms and brain circuits that enable the switching of the valence of memories remain largely unknown. Here we investigated these mechanisms by applying the recently developed memory engram cell- manipulation technique. We labelled with channelrhodopsin-2 (ChR2) a population of cells in either the dorsal dentate gyrus (DG) of the hippocampus or the basolateral complex of the amygdala (BLA) that were specifically activated during contextual fear or reward conditioning. Both groups of fear-conditioned mice displayed aversive light-dependent responses in an optogenetic place avoidance test, whereas both DG- and BLA-labelled mice that underwent reward conditioning exhibited an appetitive response in an optogenetic place preference test. Next, in an attempt to reverse the valence of memory within a subject, mice whose DG or BLA engram had initially been labelled by contextual fear or reward conditioning were subjected to a second conditioning of the opposite valence while their original DG or BLA engram was reactivated by blue light. Subsequent optogenetic place avoidance and preference tests revealed that although the DG-engram group displayed a response indicating a switch of the memory valence, the BLA-engram group did not. This switch was also evident at the cellular level by a change in functional connectivity between DG engram-bearing cells and BLA engram-bearing cells. Thus, we found that in the DG, the neurons carrying the memory engram of a given neutral context have plasticity such that the valence of a conditioned response evoked by their reactivation can be reversed by re-associating this contextual memory engram with a new unconditioned stimulus of an opposite valence. Our present work provides new insight into the functional neural circuits underlying the malleability of emotional memory.RIKEN Brain Science InstituteHoward Hughes Medical InstituteJPB FoundationNational Institutes of Health (U.S.) (Pre-doctoral Training Grant T32GM007287

Biological Contribution to Social Influences on Alcohol Drinking: Evidence from Animal Models

Social factors have a tremendous influence on instances of heavy drinking and in turn impact public health. However, it is extremely difficult to assess whether this influence is only a cultural phenomenon or has biological underpinnings. Research in non-human primates demonstrates that the way individuals are brought up during early development affects their future predisposition for heavy drinking, and research in rats demonstrates that social isolation, crowding or low social ranking can lead to increased alcohol intake, while social defeat can decrease drinking. Neurotransmitter mechanisms contributing to these effects (i.e., serotonin, GABA, dopamine) have begun to be elucidated. However, these studies do not exclude the possibility that social effects on drinking occur through generalized stress responses to negative social environments. Alcohol intake can also be elevated in positive social situations, for example, in rats following an interaction with an intoxicated peer. Recent studies have also begun to adapt a new rodent species, the prairie vole, to study the role of social environment in alcohol drinking. Prairie voles demonstrate a high degree of social affiliation between individuals, and many of the neurochemical mechanisms involved in regulation of these social behaviors (for example, dopamine, central vasopressin and the corticotropin releasing factor system) are also known to be involved in regulation of alcohol intake. Naltrexone, an opioid receptor antagonist approved as a pharmacotherapy for alcoholic patients, has recently been shown to decrease both partner preference and alcohol preference in voles. These findings strongly suggest that mechanisms by which social factors influence drinking have biological roots, and can be studied using rapidly developing new animal models

β-Adrenoreceptor Stimulation Mediates Reconsolidation of Social Reward-Related Memories

In recent years, the notion that consolidated memories become transiently unstable after retrieval and require reconsolidation to persist for later use has received strong experimental support. To date, the majority of studies on reconsolidation have focused on memories of negative emotions, while the dynamics of positive memories have been less well studied. Social play, the most characteristic social behavior displayed by young mammals, is important for social and cognitive development. It has strong rewarding properties, illustrated by the fact that it can induce conditioned place preference (CPP). In order to understand the dynamics of positive social memories, we evaluated the effect of propranolol, a β-adrenoreceptor antagonist known to influence a variety of memory processes, on acquisition, consolidation, retrieval and reconsolidation of social play-induced CPP in adolescent rats.Systemic treatment with propranolol, immediately before or after a CPP test (i.e. retrieval session), attenuated CPP 24 h later. Following extinction, CPP could be reinstated in saline--but not in propranolol-treated rats, indicating that propranolol treatment had persistently disrupted the CPP memory trace. Propranolol did not affect social play-induced CPP in the absence of memory retrieval or when administered 1 h or 6 h after retrieval. Furthermore, propranolol did not affect acquisition, consolidation or retrieval of social play-induced CPP.We conclude that β-adrenergic neurotransmission selectively mediates the reconsolidation, but not other processes involved in the storage and stability of social reward-related memories in adolescent rats. These data support the notion that consolidation and reconsolidation of social reward-related memories in adolescent rats rely on distinct neural mechanisms

Maternal Environment Influences Cocaine Intake in Adulthood in a Genotype-Dependent Manner

Background: Accumulating epidemiological evidence points to the role of genetic background as a modulator of the capacity of adverse early experiences to give rise to mental illness. However, direct evidence of such gene-environment interaction in the context of substance abuse is scarce. In the present study we investigated whether the impact of early life experiences on cocaine intake in adulthood depends on genetic background. In addition, we studied other behavioral dimensions associated with drug abuse, i.e. anxiety- and depression-related behaviors. Methodology/Principal Findings: For this purpose, we manipulated the maternal environment of two inbred mouse strains, the C57BL/6J and DBA/2J by fostering them with non-related mothers, i.e. the C3H/HeN and AKR strains. These mother strains show respectively high and low pup-oriented behavior. As adults, C57BL/6J and DBA/2J were tested either for cocaine intravenous self-administration or in the elevated plus-maze and forced swim test (FST). We found that the impact of maternal environment on cocaine use and a depression-related behavior depends upon genotype, as cocaine self-administration and behavior in the FST were influenced by maternal environment in DBA/2J, but not in C57BL/6J mice. Anxiety was not influenced by maternal environment in either strain. Conclusions/Significance: Our experimental approach could contribute to the identification of the psychobiological factor

Effects of a selective mu opioid receptor agonist and naloxone on the intake of sodium chloride solutions

Endogenous opioid peptides are thought to play a role in mediating the palatability or rewarding aspects of sweet tastes. There is also evidence, however, which suggests that opioids may influence the preference for the taste of salt as well. In the present studies, we measured the effects of central administration of naloxone and the mu agonist [ d -Ala 2 ,MePhe 4 ,Gly-ol 5 ]enkephalin (DAGO) on the ingestion of salt solutions. In non-deprived rats given a choice of water and 0.6% saline, ICV injections of DAGO (1 and 3 nmol) significantly increased the intake of 0.6% saline; baseline water intake was minimal and was unaffected by DAGO. When rats were given a choice between water and 1.7% saline, DAGO stimulated both water and saline intake. Because 1.7% saline is a hypertonic solution, the increase in water intake may have been secondary to saline intake. In rats on a deprivation schedule in which water and 0.6% saline were available for only 2–3 h/day, there was a tendency for DAGO to increase 0.6% saline intake and decrease water intake, though these effects were not significant. In rats given water and 1.7% saline, DAGO increased saline intake and had no effect on water intake. Naloxone was also tested in water-deprived rats. Naloxone (20 and 50 µg) significantly decreased 0.6% saline intake; baseline water intake was low (3–5 ml) and was unaffected by naloxone. When rats were given a choice between water and 1.7% saline, naloxone (50 µg) significantly reduced water intake, while intake of 1.7% saline was slightly increased. These results suggest a role for central mu opioid receptors in mediating the preference for salt solutions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46331/1/213_2005_Article_BF02245792.pd

Effects of a bee pollen dieton the growth of the laboratory rat

American Bee Journal, 139(5):390-395, 1999 künyesinde yer alan bu makale Mustafa Civan tarafından Türkçe'ye tercüme edilmiştir.Laboratuvarımızdaki çalışmalar sadece su ve polenle beslenen sıçanların 3 farklı akrabalı çiftle­ şen hattın 1 yıl ya da daha uzun süreyle incelendiğinde polenin (ki bu polenler ticari firmalar tarafından s atılan ve özellikleri belli olan polenlerdir), sıçanların sağlıklarının klinik seviyede korunması için ge­rekli besleyici bütün bileşenleri içermekte olduğunu göstermiştir, (Liebelt, R. A. ve ark. 1994). Yine su ve polenle beslenen bu sıçanların , incelenen 30-90 gün vücut ve organ gelişimlerinin , standart laboratuvar pelet yemi ile beslenen kontrol sıçanlarının aynı süredeki vücut ve organ gelişimleri ile aynı olduğu gözlenmiştir. Bu çalışmanın amacı , 12 haftalık süre içerisinde kontollü laboratuvar şartları altın­daki sıçanların hızlı gelişiminde su ve polen diyetinin etkisi olup olmadığını ortaya çıkarmaktır. Bu çalışma için dişi ve erkek Sprague Dawley fareleri kullanılmıştır. Kontrol fareleri Purina Lablox laboratuvar pelet yemi ile beslenirken, araştırılan fareler doğal polen granülleri ile beslenmiştir. Tüm hayvanlar 12 haftalık çalışma boyunca klinik olarak sağlıklı bir seviyede kalmışlardır. Kontrol grubu farelerinin hem erkekleri hem de dişileri polenle beslenenlere göre daha büyük bir fiziksel duru­ma gelmişlerdir. Polenle beslenen farelerin görüntüsü daha sağlıklı, vücut tüyleri ise daha canlı ve parlaktır. Toplam vücut ağırlıklarının her 100 gramına karşılık gelen toplam organ ağırlıklarında (ki toplam organ ağırlığından kasıt ; akciğer, karaciğer , bağırsaklar ve mide, böbrekler, gastrocnemius kası ve adrenal bezlerinin oluşturduğu toplam ağırlıktır) belirgin bir farklılık görülmemiştir, yani oran olarak aşağı yukarı aynıdır. Polenle beslenen dişi farelerin kalpleri, kontrol grubu dişi farelerinin kalplerinden daha ağırdır, ama aynı durum erkek farelerde görülmemiştir. İlginç bir başka durum ise polenle bes­lenen hem erkek hem dişi farelerin beyinlerinin, kontrol grubu farelerinin beyinlerinden daha ağır olmasıdır. Her iki grubun erkekleri ve dişileri arasında en dikkat çeken farklılık inguinal ve gonadal yağ depolarının yağ içeriğidir ki bu da farelerin toplam vücut yağ içerikleriyle ilişkilidir. Po­lenle beslenen erkek farelerin her iki yağ deposundaki yağ miktarı , kontrol grubu erkekleriyle karşılaştı­rıldığında belirgin bir şekilde daha azdır. Dişilerin rahim ve yumurtalık ağırlıklarında belirgin bir farklılık yokken , polenle beslenen erkek farelerin testisleri, kontrol grubu erkek farelerinin testislerine göre belirgin bir şekilde ağırdır. Akyuvar hücre sayıları, hemoglobin konsantrasyonu ve alyuvar hücrelerinin kandaki oranı ve ortalama corpuscular miktarı açısından her iki grubun erkekleri arasında belirgin bir farklılık görülme­miştir. Her iki grubun erkeklerinin kanlarının kimyasal analizi; sodyum, potasyum, klorid, glikoz, kan üresi, nitrojen, ürik asit, fosfor, kalsiyum, toplam protein ve albumin seviyelerinin aşağı yukarı aynı olduğunu göstermiştir. Fakat polenle beslenen erkek farelerin serum kolesterol seviyelerinin kontrol grubu erkek farelerininkinden yaklaşık %50 düşük olduğu belirlenmiştir. Sonuç olarak bu çalışma; özellikleri belli olan ve ticari olarak satılan polenlerin laboratuvar fare ve sıçanlarda tek besin kaynağı olarak kullanıldığında herhangi bir zararlı etkiye ya da organlarda hasara yol açmadan vücudun normal gelişimini ve büyümesini sağladığı ve bunun için gerekli tüm elementleri içerdiği hipotezini desteklemektedir