Declarative Memory Formation Research Articles

Anatomical and electrophysiological analysis of the fasciola cinerea of the mouse hippocampus.

The hippocampus is considered essential for several forms of declarative memory, including spatial and social memory. Despite the extensive research of the classic subfields of the hippocampus, the fasciola cinerea (FC)-a medially located structure within the hippocampal formation-has remained largely unexplored. In the present study, we performed a morpho-functional characterization of principal neurons in the mouse FC. Using in vivo juxtacellular recording of single neurons, we found that FC neurons are distinct from neighboring CA1 pyramidal cells, both morphologically and electrophysiologically. Specifically, FC neurons displayed non-pyramidal morphology and granule cell-like apical dendrites. Compared to neighboring CA1 pyramidal neurons, FC neurons exhibited more regular in vivo firing patterns and a lower tendency to fire spikes at short interspike intervals. Furthermore, tracing experiments revealed that the FC receives inputs from the lateral but not the medial entorhinal cortex and CA3, and it provides a major intra-hippocampal projection to the septal CA2 and sparser inputs to the distal CA1. Overall, our results indicate that the FC is a morphologically and electrophysiologically distinct subfield of the hippocampal formation; given the established role of CA2 in social memory and seizure initiation, the unique efferent intra-hippocampal connectivity of the FC points to possible roles in social cognition and temporal lobe epilepsy.

Differential effects of clonazepam on declarative memory formation and face recognition

Benzodiazepines are commonly used drugs to treat anxiety in crime witnesses. These increase GABA inhibitory effects, which impairs aversive memory encoding and consolidation. Eyewitness memory is essential in justice. However, memory is malleable leading to false memories that could cause a selection of an innocent in a lineup. Here, we studied whether a low dose of Clonazepam impairs memory encoding as well as consolidation of faces and narrative of the event. We performed two experiments using a double-blind and between subject design (N = 216). Day 1: subjects watched a crime video and received Clonazepam 0.25 mg (CLZ group) or placebo (PLC group) before (Exp. 1) or after the video (Exp. 2) to assess the effect on encoding and consolidation. One week later, the memory was assessed using a present and absent target lineup and asking for a free recall. Regarding encoding, we found that in the CLZ group memory was impaired in the free recall task, while no differences were found for recognition memory. Regarding consolidation, we did not observe memory measures that were affected by this dose of benzodiazepines. The results suggest that while some aspects of eyewitness memory could be modulated even with low doses of benzodiazepine, others could not be affected. More studies should be performed with higher doses of CLZ similar to those administered in real life. These results are relevant in the judicial field to assess the reliability of the eyewitness elections under the effects of this drug.

Drawing improves memory in patients with hippocampal damage.

The hippocampus plays a critical role in the formation of declarative memories, and hippocampal damage leads to significant impairments in new memory formation. Drawing can serve as a form of multi-modal encoding that improves declarative memory performance relative to other multimodal encoding strategies such as writing. We examined whether, and to what extent, patients with hippocampal damage could benefit from the mnemonic strategy of drawing. Three patients with focal hippocampal damage, and one patient with both hippocampal and cortical lesions, in addition to 22 age-, sex-, and education-matched controls, were shown a list of words one at a time during encoding and instructed to either draw a picture or repeatedly write each word for 40 s. Following a brief filled delay, free recall and recognition memory for words from both encoding trial types were assessed. Controls showed enhanced recall and recognition memory for words drawn versus those that were written, an effect that was even more pronounced in patients with focal hippocampal damage. By contrast, the patient with both hippocampal and cortical lesions showed no drawing-mediated boost in either recall or recognition memory. These findings demonstrate that drawing is an effective encoding strategy, likely accruing from the engagement of extra-hippocampal processes including the integration of cortical-based motor, visual, and semantic processing, enabling more elaborative encoding.

Non-linear susceptibility to interferences in declarative memory formation.

After encoding, memories go through a labile state followed by a stabilization process known as consolidation. Once consolidated they can enter a new labile state after the presentation of a reminder of the original memory, followed by a period of re-stabilization (reconsolidation). During these periods of lability the memory traces can be modified. Currently, some studies show a rapid stabilization after 30 min, while others show that stabilization occurs after longer periods (e.g. > 6 h). Here we investigate the effect of an interference treatment on declarative memory consolidation, comparing distinct time intervals after acquisition. On day 1, participants learned a list of non- syllable pairs (List 1). 5 min, 30 min, 3 h or 8 h later, they received an interference list (List 2) that acted as an amnesic agent. On day 2 (48 h after training) participants had to recall List 1 first, followed by List 2. We found that the List 1 memory was susceptible to interference when List 2 was administered 5 min or 3 h after learning but not when it was administered 30 min or 8 h after. We propose the possibility that this rapid memory protection could be induced by a fast and transient neocortical integration. Our results open a discussion about the contribution of molecular and systemic aspects to memory consolidation.

A tradeoff between musical tension perception and declarative memory.

Successful formation of long-term declarative memory is influenced, among other things, by attention, emotion, and deviation from expectations. A unique form of expectation can be elicited through musical tension, evoked by the prolongation of certain musical progressions. We examined the effect that musical tension exerts on the formation of declarative memory, by composing three original music pieces that contained tension segments, achieved by delays in release from dominant to tonic harmonies. Music-evoked tension was validated using music information retrieval (MIR) analysis, as well as skin conductance response (SCR) measures. Indeed, tension-evoking musical excerpts were associated with heightened SCR, corroborated by increased subjective ratings of tension, as compared to neutral excerpts. In the main experiment, 50 participants listened to the three musical pieces while they were presented with unique images that were randomly assigned to four conditions: tension, tension-release, neutral music, and silence. One day later, their memory for the images was examined using a recognition test. We found that memory performance was enhanced for images presented during both neutral and tense music compared to silence. Moreover, we observed a tradeoff effect between post-experiment tension perception and memory, such that individuals who perceived musical tension as such displayed reduced memory performance for images encoded during musical tension, whereas tense music benefited memory for those with lower musical tension perception. Understanding the interrelations between musical components, which exert powerful and fundamental responses in humans, and cognitive faculties, may provide insights as to the basic features of memory formation.Supplementary InformationThe online version contains supplementary material available at 10.3758/s13423-022-02095-z.

Enhanced declarative memory in long-term mindfulness practitioners.

Mindfulness meditation (MM) practice is considered to benefit physical and mental health. In particular, several studies have shown a beneficial effect of MM practice on memory performance. However, it is still not clear how long-term training affects long-term declarative memory. In this study we aimed to examine whether long-term MM training impacts declarative memory formation for diverse memoranda types, as well as the role of trait mindfulness, and the possible mediating role of anxiety. We examined long-term memory performance in 23 experienced MM practitioners and 22 meditation-naïve age-matched individuals, by administering a variety of declarative memory tests, ranging from item recognition to narrative and autobiographical memory recollection and future projection. The participants also filled the Five Facet MindfulnessQuestionnaire (FFMQ) and State-Trait Anxiety Inventory (STAI). Compared to the control group, long-term MM practitioners exhibited heightened memory performance for the picture recognition test and experienced enhanced vividness during autobiographic memory retrieval and future simulations. We also report a significant trait mindfulness and memory performance correlation, stemming exclusively from the Mm group. Our findings extend previous reports of the beneficial effect of a short-term MM training on memory performance, by showing the beneficial effect of long-term training on declarative memory. We also provide initial evidence that trait mindfulness is positively correlated with declarative memory performance, as a function of MM practice, and discuss these findings in light of the role of self-mode and cognitive diffusion, as well as attention and emotion.

Transient Destabilization of Declarative Memory-Opposing Impact of Physical Exercise or Rest after Encoding in Typically Developing Children and Children with Attention Deficit Hyperactivity Disorder but No Difference after Subsequent Sleep.

Background: Children are especially sensitive to a broad range of influences and show a remarkable capacity for learning. One prominent example is declarative memory, which may be influenced by a variety of factors and is impaired in attention deficit hyperactivity disorder (ADHD). Exercise and sleep, or both combined, might foster declarative memory. Methods: Here, 12 typically developing children (TDC) and 12 age-matched children with ADHD participated in an exercise and rest condition before a night in the sleep laboratory. Declarative memory was encoded before exercise or rest and retrieved before and after a night of sleep. Results: Exercise in TDC but rest in ADHD lead to a transient destabilization of declarative memory, while there were no more differences after a night of sleep. Rapid eye movement (REM) sleep latency was prolonged after exercise in both groups. Conclusions: Exercise leads to opposing effects on immediate declarative memory formation. The factors or contexts that promote or hinder declarative memory formation in children ADHD and TDC differ, and further work is needed to determine the recommendations for declarative learning in children with ADHD.

A direct lateral entorhinal cortex to hippocampal CA2 circuit conveys social information required for social memory

The hippocampus is essential for different forms of declarative memory, including social memory, the ability to recognize and remember a conspecific. Although recent studies identify the importance of the dorsal CA2 region of the hippocampus in social memory storage, little is known about its sources of social information. Because CA2, like other hippocampal regions, receives its major source of spatial and non-spatial information from the medial and lateral subdivisions of entorhinal cortex (MEC and LEC), respectively, we investigated the importance of these inputs for social memory. Whereas MEC inputs to CA2 are dispensable, the direct inputs to CA2 from LEC are both selectively activated during social exploration and required for social memory. This selective behavioral role of LEC is reflected in the stronger excitatory drive it provides to CA2 compared with MEC. Thus, a direct LEC → CA2 circuit is tuned to convey social information that is critical for social memory.

Distinct Effects of Acute Aerobic Exercise on Declarative Memory and Procedural Memory Formation.

Objective: To investigate the different effects of acute aerobic exercise on the formation of long-term declarative memory (DM) and procedural memory (PM). Methods: Twenty-two young men completed DM and PM tasks under three experimental conditions: pre-acquisition exercise, post-acquisition exercise, and no exercise (control). The DM task encompassed word learning, free recall tests both immediately and 1 h later, and a recognition test conducted 24 h after word learning. A serial reaction time task (SRTT) was utilized to assess exercise effects on PM. The SRTT included a sequence learning phase followed by sequence tests 1 h and 24 h later. The exercise program consisted of 30 min of moderate-intensity aerobic exercise. Results: In the DM task, compared to the control condition, pre-acquisition exercise, but not post-acquisition exercise, enhanced free recall performance significantly 1 h and 24 h later. The target word recognition rate and discriminative index (d′) of the recognition test were significantly enhanced in both exercise conditions compared to the control condition. In the PM task, we observed significantly reduced (improved) reaction times at the 24-h test in the post-acquisition exercise condition compared to in the control condition. Conclusion: Acute aerobic exercise may enhance long-term DM and PM via effects on different processing periods. For DM, exercise had a pronounced effect during the encoding period, whereas for PM, exercise was found to have an enhancing effect during the consolidation period.

A-075 A Case Study of Anterograde Memory Impairment Following Forniceal Infarct– Neurocognitive Sequelae and Recovery

Abstract Objective To describe neurobehavioral consequences and recovery course in a case of acute infarct of the fornix superimposed on chronic subcortical cerebrovascular disease. Method We present a right-handed, 72-year-old, African American man with cardiovascular risk factors, chronic kidney disease, and history of CVA with no prior functional or cognitive difficulties. He was evaluated twice, first four days post and again two months post-infarct of the bilateral fornix. Results Initial inpatient testing revealed impaired verbal memory characterized by rapid forgetting (HVLT-R Delay T = < 20) with some benefit from recognition cues, and subtle deficits in constructional praxis and practical judgement. On repeat evaluation at four months post-stroke, he demonstrated memory impairment across modalities (HVLT-R Delay T = < 20, BVMT-R Delay T = < 20) with marginal benefit from context and cues. He required assistance with multiple instrumental activities of daily living (e.g., financial and healthcare management) and displayed anosognosia of both cognitive and functional deficits. Conclusion This case illustrates the role of the fornix in the process of memory encoding and self-awareness. Literature describing the neurobehavioral role of the fornix is sparse, however, it has been implicated in episodic memory functions due to hippocampal connectivity. This case study further implicates the fornix in declarative memory formation and will add to the literature by detailing a specific cognitive profile that may inform planning for recovery and rehabilitation.

Sleep-dependent memory consolidation in infants protects new episodic memories from existing semantic memories

Any experienced event may be encoded and retained in detail as part of our episodic memory, and may also refer and contribute to our generalized knowledge stored in semantic memory. The beginnings of this declarative memory formation are only poorly understood. Even less is known about the interrelation between episodic and semantic memory during the earliest developmental stages. Here, we show that the formation of episodic memories in 14- to 17-month-old infants depends on sleep, subsequent to exposure to novel events. Infant brain responses reveal that, after sleep-dependent consolidation, the newly stored events are not processed semantically, although appropriate lexical-semantic memories are present and accessible by similar events that were not experienced before the nap. We propose that temporarily disabled semantic processing protects precise episodic memories from interference with generalized semantic memories. Selectively restricted semantic access could also trigger semantic refinement, and thus, might even improve semantic memory.

Deficit in hippocampal ripples does not preclude spatial memory formation in APP/PS1 mice

General theory of declarative memory formation posits a cortical-hippocampal dialog during which hippocampal ripple oscillations support information transfer and long-term consolidation of hippocampus dependent memories. Brain dementia, as Alzheimer disease (AD), is accompanied by memory loss and inability to form new memories. A large body of work has shown variety of mechanisms acting at cellular and molecular levels which can putatively play an important role in the impairment of memory formation. However, far less is known about changes occurring at the network-level activity patterns that support memory processing. Using freely moving APP/PS1 mice, a model of AD, we undertook a study to unravel the alterations of the activity of hippocampal and cortical circuits during generation of ripples in the transgenic and wild-type mice undergoing encoding and consolidation of spatial information. We report that APP/PS1 animals are able to consolidate spatial memory despite a major deficit of hippocampal ripples occurrence rate and learning dependent dynamics. We propose that these impairments may be compensated by an increase of the occurrence of cortical ripples and reorganization of cortical-hippocampal interaction.

Positive allosteric modulation of the α7 nicotinic acetylcholine receptor as a treatment for cognitive deficits after traumatic brain injury.

Cognitive impairments are a common consequence of traumatic brain injury (TBI). The hippocampus is a subcortical structure that plays a key role in the formation of declarative memories and is highly vulnerable to TBI. The α7 nicotinic acetylcholine receptor (nAChR) is highly expressed in the hippocampus and reduced expression and function of this receptor are linked with cognitive impairments in Alzheimer's disease and schizophrenia. Positive allosteric modulation of α7 nAChRs with AVL-3288 enhances receptor currents and improves cognitive functioning in naïve animals and healthy human subjects. Therefore, we hypothesized that targeting the α7 nAChR with the positive allosteric modulator AVL-3288 would enhance cognitive functioning in the chronic recovery period of TBI. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury or sham surgery. At 3 months after recovery, animals were treated with vehicle or AVL-3288 at 30 min prior to cue and contextual fear conditioning and the water maze task. Treatment of TBI animals with AVL-3288 rescued learning and memory deficits in water maze retention and working memory. AVL-3288 treatment also improved cue and contextual fear memory when tested at 24 hr and 1 month after training, when TBI animals were treated acutely just during fear conditioning at 3 months post-TBI. Hippocampal atrophy but not cortical atrophy was reduced with AVL-3288 treatment in the chronic recovery phase of TBI. AVL-3288 application to acute hippocampal slices from animals at 3 months after TBI rescued basal synaptic transmission deficits and long-term potentiation (LTP) in area CA1. Our results demonstrate that AVL-3288 improves hippocampal synaptic plasticity, and learning and memory performance after TBI in the chronic recovery period. Enhancing cholinergic transmission through positive allosteric modulation of the α7 nAChR may be a novel therapeutic to improve cognition after TBI.

White-matter commissures: a clinically focused anatomical review.

The objective of this review is to provide a structured approach to the main white matter commissures, their anatomic and radiological definition and disease implications. The Pubmed database and The JAMA Network were used for the literature review and the following terms were searched using Sort by: Best Match and Sort by: Most Recent: telencephalic commissure, forebrain commissure anatomy, fornix anatomy, commissure of fornix, posterior commissure, corpus callosum, commissural agenesis, Probst bundle, corpus callosum disorders review, corpus callosum diseases review, Marchiafava-Bignami, Alzheimer's disease and Forel commissure; 36 papers were selected, one excluded due to the language barrier. The interhemispheric communication in the brain is achieved via the brain commissures, bundles of white matter linking the two cerebral hemispheres. Anterior white commissure (AWC)-related with olfactory and non-visual communication, hippocampal commissure-main efferent pathway of the hippocampus, connecting the hippocampal formation to structures beyond the temporal lobe, crucial in declarative memory formation and consolidation-and the corpus callosum (CC)-from the anterior commissure to the hippocampal commissure-are the main telencephalic commissures. Supramammilary commissure, posterior commissure, supraoptic commissure and habenular commissure are diencephalic commissures-unknown function, probably related to involuntary eye movements. Commissural agenesis (AWC is absent or impossible to recognize), Alzheimer's Disease (hippocampal commissure may contribute for disease dissemination) and agenesis of corpus callosum are some of the disturbances that involve the telenchephalic commissures. A comprehensive understanding of the clinic-anatomic correlation is pivotal to understand the pathology and therefore improve our diagnostic accuracy and treatment options, in the background of all patient management.

Previously rewarding environments enhance incidental memory formation.

Declarative memory performance is superior for items that were encoded in temporal proximity to reward delivery or expectancy. How reward-predicting contexts affect subsequent declarative memory formation in those contexts are, however, unknown. Using an ecological experimental setup in the form of a naturalistic driving simulator task, we examined the effect that previously rewarded environments may have on incidental memory formation. After driving in two distinct environments, one of which associated with monetary reward, participants drove again in the environments, which were embedded with unique images on billboards. A recognition test 24 h later demonstrated that incidental memory was superior for items presented in the reward-associated environment. These findings suggest that environmental cues imbued with incentive salience promote memory processes even in the absence of reward.

Hippocampal area CA2: an emerging modulatory gateway in the hippocampal circuit.

The hippocampus is a critical brain region for the formation of declarative memories. While social memory had long been attributed to be a function of the hippocampus, it is only of late that the area CA2 of the hippocampus was demarcated as essential for social memory formation. In addition to this distinct role, CA2 possesses unique molecular, structural and physiological characteristics compared to the other CA regions-CA1 and CA3, and the dentate gyrus (DG). CA2 pyramidal neurons are positioned at a location between CA1 and CA3, receiving inputs from CA3 and DG, in addition to forming a powerful disynaptic circuit with direct input from the entorhinal cortical layer II neurons. CA2 also receives direct inputs from the hypothalamic regions and displays a unique expression pattern for receptors for neuromodulators. The location, inputs, and molecular signatures of the area CA2 point to the possibility that CA2 serves as a modulatory gateway that processes information from the entorhinal cortex and CA3, before relaying them onto CA1, the major output of the hippocampus. This review discusses recent findings regarding plasticity and neuromodulation in the CA2 region of the hippocampus, and how this may have the potential to influence plasticity in connecting circuits, and thereby memory and behaviour.

Protocols to Study Declarative Memory Formation in Mice and Humans:Optogenetics and Translational Behavioral Approaches.

Declarative memory formation depends on the hippocampus and declines in aging. Two functions of the hippocampus, temporal binding and relational organization (Rawlins and Tsaltas, 1983; Eichenbaum et al., 1992 ; Cohen et al., 1997 ), are known to decline in aging (Leal and Yassa, 2015). However, in the literature distinct procedures have been used to study these two functions. Here, we describe the experimental procedures used to investigate how these two processes are related in the formation of declarative memory and how they are compromised in aging ( Sellami et al., 2017 ). First, we studied temporal binding using a one-trial learning procedure: trace fear conditioning. It is classical Pavlovian conditioning requiring temporal binding since a brief temporal gap separates the conditioned stimulus (CS) and unconditioned stimulus (US) presentations. We combined the trace fear condition procedure with an optogenetic approach, and we showed that the temporal binding relies on dorsal (d)CA1 activity over temporal gaps. Then, we studied the interaction between temporal binding and relational organization in declarative memory formation using a two-phase radial-maze task in mice and its virtual analog in humans. The behavioral procedure comprises an initial learning phase where subjects learned the constant rewarding /no rewarding valence of each arm, followed by a test phase where the reward contingencies among the arms remained unchanged but where the arms were recombined to assess flexibility, a cardinal property of declarative memory. We demonstrated that dCA1-dependent temporal binding is necessary for the development of a relational organization of memories that allows flexible declarative memory expression. Furthermore, in aging, the degradation of declarative memory is due to a reduction of temporal binding capacity that prevents relation organization.

Current Topics Regarding the Function of the Medial Temporal Lobe Memory System.

The first clear insight that the medial temporal lobe of the human brain was in fact a system of anatomically connected structures that were organized into a memory system came in 1957 from the observations by Brenda Milner of the noted amnesic patient H.M. Subsequent work in humans, monkeys, and rodents has identified all of the components of the medial temporal lobe (MTL) that formed the memory system. Currently, work is ongoing to identify the specific contributions each structure in the medial temporal lobe makes towards the formation and storage of long-term declarative memory. The historical background of this work is described including what insights the study of noted neurologic patients H.M. and E.P. provided for understanding the function of the medial temporal lobe. The development of an animal model of medial temporal lobe function is described. Additionally, the insights that lead to the understanding that the brain contains multiple, anatomically discrete, memory systems are described. Finally, three current topics of debate are addressed: First, does the perirhinal cortex exclusively support memory, or does it support both memory and higher order visual perception? Second, is there an anatomical separation between recollection and familiarity ? Third, is the organization of spatial memory different between humans and rats, or perhaps the difference is between the working memory capacities of the two species?

Human aging reduces the neurobehavioral influence of motivation on episodic memory

The neural circuitry mediating the influence of motivation on long-term declarative or episodic memory formation is delineated in young adults, but its status is unknown in healthy aging. We examined the effect of reward and punishment anticipation on intentional declarative memory formation for words using an event-related functional magnetic resonance imaging (fMRI) monetary incentive encoding task in twenty-one younger and nineteen older adults. At 24-hour memory retrieval testing, younger adults were significantly more likely to remember words associated with motivational cues than neutral cues. Motivational enhancement of memory in younger adults occurred only for recollection (“remember” responses) and not for familiarity (“familiar” responses). Older adults had overall diminished memory and did not show memory gains in association with motivational cues. Memory encoding associated with monetary rewards or punishments activated motivational (substantia nigra/ventral tegmental area) and memory-related (hippocampus) brain regions in younger, but not older, adults during the target word periods. In contrast, older and younger adults showed similar activation of these brain regions during the anticipatory motivational cue interval. In a separate monetary incentive delay task that did not require learning, we found evidence for relatively preserved striatal reward anticipation in older adults. This supports a potential dissociation between incidental and intentional motivational processes in healthy aging. The finding that motivation to obtain rewards and avoid punishments had reduced behavioral and neural influence on intentional episodic memory formation in older compared to younger adults is relevant to life-span theories of cognitive aging including the dopaminergic vulnerability hypothesis.

Temporal binding function of dorsal CA1 is critical for declarative memory formation

Temporal binding, the process that enables association between discontiguous stimuli in memory, and relational organization, a process that enables the flexibility of declarative memories, are both hippocampus-dependent and decline in aging. However, how these two processes are related in supporting declarative memory formation and how they are compromised in age-related memory loss remain hypothetical. We here identify a causal link between these two features of declarative memory: Temporal binding is a necessary condition for the relational organization of discontiguous events. We demonstrate that the formation of a relational memory is limited by the capability of temporal binding, which depends on dorsal (d)CA1 activity over time intervals and diminishes in aging. Conversely, relational representation is successful even in aged individuals when the demand on temporal binding is minimized, showing that relational/declarative memory per se is not impaired in aging. Thus, bridging temporal intervals by dCA1 activity is a critical foundation of relational representation, and a deterioration of this mechanism is responsible for the age-associated memory impairment.