Homiletics: Outlines on the Swedish Gospels (Alternate Series)

Outlines on the Swedish Gospels (Alternate Series

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

Two years later – Revisiting autobiographical memory representations in vmPFC and hippocampus

A long-standing question in memory neuroscience concerns how and where autobiographical memories of personal experiences are represented in the brain. In a previous high resolution multivoxel pattern analysis fMRI study, we examined two week old (recent) and ten year old (remote) autobiographical memories (Bonnici et al., 2012, J. Neurosci. 32:16982–16991). We found that remote memories were particularly well represented in ventromedial prefrontal cortex (vmPFC) compared to recent memories. Moreover, while both types of memory were represented within anterior and posterior hippocampus, remote memories were more easily distinguished in the posterior portion. These findings suggested that a change of some kind had occurred between two weeks and ten years in terms of where autobiographical memories were represented in the brain. In order to examine this further, here participants from the original study returned two years later and recalled the memories again. We found that there was no difference in the detectability of memory representations within vmPFC for the now 2 year old and 12 year old memories, and this was also the case for the posterior hippocampus. Direct comparison of the two week old memories (original study) with themselves two years later (present study) confirmed that their representation within vmPFC had become more evident. Overall, this within-subjects longitudinal fMRI study extends our understanding of autobiographical memory representations by allowing us to narrow the window within which their consolidation is likely to occur. We conclude that after a memory is initially encoded, its representation within vmPFC has stablised by, at most, two years later

Forgetting, Reminding, and Remembering: The Retrieval of Lost Spatial Memory

Retrograde amnesia can occur after brain damage because this disrupts sites of storage, interrupts memory consolidation, or interferes with memory retrieval. While the retrieval failure account has been considered in several animal studies, recent work has focused mainly on memory consolidation, and the neural mechanisms responsible for reactivating memory from stored traces remain poorly understood. We now describe a new retrieval phenomenon in which rats' memory for a spatial location in a watermaze was first weakened by partial lesions of the hippocampus to a level at which it could not be detected. The animals were then reminded by the provision of incomplete and potentially misleading information—an escape platform in a novel location. Paradoxically, both incorrect and correct place information reactivated dormant memory traces equally, such that the previously trained spatial memory was now expressed. It was also established that the reminding procedure could not itself generate new learning in either the original environment, or in a new training situation. The key finding is the development of a protocol that definitively distinguishes reminding from new place learning and thereby reveals that a failure of memory during watermaze testing can arise, at least in part, from a disruption of memory retrieval