Sonja Blum

Bio: Sonja Blum is an academic researcher from New York University. The author has contributed to research in topics: Hippocampus & Long-term memory. The author has an hindex of 11, co-authored 17 publications receiving 1122 citations. Previous affiliations of Sonja Blum include University of Texas Health Science Center at Houston & Columbia University.

A Mitogen-Activated Protein Kinase Cascade in the CA1/CA2 Subfield of the Dorsal Hippocampus Is Essential for Long-Term Spatial Memory

Abstract: Behavioral, biophysical, and pharmacological studies have implicated the hippocampus in the formation and storage of spatial memory. However, the molecular mechanisms underlying long-term spatial memory are poorly understood. In this study, we show that mitogen-activated protein kinase (MAPK, also called ERK) is activated in the dorsal, but not the ventral, hippocampus of rats after training in a spatial memory task, the Morris water maze. The activation was expressed as enhanced phosphorylation of MAPK in the pyramidal neurons of the CA1/CA2 subfield. In contrast, no increase in the percentage of phospho-MAPK-positive cells was detected in either the CA3 subfield or the dentate gyrus. The enhanced phosphorylation was observed only after multiple training trials but not after a single trial or after multiple trials in which the location of the target platform was randomly changed between each trial. Inhibition of the MAPK/ERK cascade in dorsal hippocampi did not impair acquisition, but blocked the formation of long-term spatial memory. In contrast, intrahippocampal infusion of SB203580, a specific inhibitor of the stress-activated MAPK (p38 MAPK), did not interfere with memory storage. These results demonstrate a MAPK-mediated cellular event in the CA1/CA2 subfields of the dorsal hippocampus that is critical for long-term spatial memory.

Regional white matter hyperintensity volume, not hippocampal atrophy, predicts incident Alzheimer disease in the community.

Abstract: Background New-onset Alzheimer disease (AD) is often attributed to degenerative changes in the hippocampus. However, the contribution of regionally distributed small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging, remains unclear. Objective To determine whether regional WMHs and hippocampal volume predict incident AD in an epidemiological study. Design A longitudinal community-based epidemiological study of older adults from northern Manhattan, New York. Setting The Washington Heights/Inwood Columbia Aging Project. Participants Between 2005 and 2007, 717 participants without dementia received magnetic resonance imaging scans. A mean (SD) of 40.28 (9.77) months later, 503 returned for follow-up clinical examination and 46 met criteria for incident dementia (45 with AD). Regional WMHs and relative hippocampal volumes were derived. Three Cox proportional hazards models were run to predict incident dementia, controlling for relevant variables. The first included all WMH measurements; the second included relative hippocampal volume; and the third combined the 2 measurements. Main Outcome Measure Incident AD. Results White matter hyperintensity volume in the parietal lobe predicted time to incident dementia (hazard ratio [HR] = 1.194; P = .03). Relative hippocampal volume did not predict incident dementia when considered alone (HR = 0.419; P = .77) or with the WMH measures included in the model (HR = 0.302; P = .70). Including hippocampal volume in the model did not notably alter the predictive utility of parietal lobe WMHs (HR = 1.197; P = .049). Conclusions The findings highlight the regional specificity of the association of WMHs with AD. It is not clear whether parietal WMHs solely represent a marker for cerebrovascular burden or point to distinct injury compared with other regions. Future work should elucidate pathogenic mechanisms linking WMHs and AD pathology.

A role for the prefrontal cortex in recall of recent and remote memories

Abstract: Declarative memories are thought to be initially stored in the hippocampus, and then transferred to the neocortex This is a key feature of the standard model of consolidation and is supported by studies reporting a requirement for activity within the neocortex for recall of remote, but not recent, hippocampal-dependent memories New evidence from our and other laboratories, however, suggests that, for trace fear conditioning, memories are stored in the rodent medial prefrontal cortex and in the hippocampus from the time of training Consistent with this, we show that activity in the medial prefrontal cortex is necessary for retrieval of recent and remote memories, suggesting that information stored in this neocortical structure from the time of training is necessary for memory recall

Memory after silent stroke: Hippocampus and infarcts both matter

Abstract: Objective: Memory decline commonly occurs among elderly individuals. This observation is often attributed to early neurodegenerative changes in the hippocampus and related brain regions. However, the contribution of vascular lesions, such as brain infarcts, to hippocampal integrity and age-associated memory decline remains unclear. Methods: We studied 658 elderly participants without dementia from a prospective, community-based study on aging and dementia who received high-resolution structural MRI. Cortical and subcortical infarcts were identified, and hippocampal and relative brain volumes were calculated following standard protocols. Summary scores reflecting performance on tasks of memory, language, processing speed, and visuospatial function were derived from a comprehensive neuropsychological battery. We used multiple regression analyses to relate cortical and subcortical infarcts, hippocampal and relative brain volume, to measures of cognitive performance in domains of memory, language, processing speed, and visuospatial ability. Results: Presence of brain infarcts was associated with a smaller hippocampus. Smaller hippocampus volume was associated with poorer memory specifically. Brain infarcts were associated with poorer memory and cognitive performance in all other domains, which was independent of hippocampus volume. Conclusions: Both hippocampal volume and brain infarcts independently contribute to memory performance in elderly individuals without dementia. Given that age-associated neurodegenerative conditions, such as Alzheimer disease, are defined primarily by impairment in memory, these findings have clinical implications for prevention and for identification of pathogenic factors associated with disease symptomatology.

Caspase activity plays an essential role in long-term memory.

Abstract: Activation of intracellular second messenger cascades has been linked to learning and memory in various organisms. Identification of down-stream targets of these second messengers that play a role in learning and memory is an active area of research. Recently, it has been reported that increases in intracellular calcium can activate a cysteine-dependent aspartate-directed protease (caspase) cascade in mice. Using an antibody that selectively recognizes activated caspase-3, we detected the presence of this enzyme in hippocampal neurons. Inhibition of caspase activity in the hippocampus blocked long-term, but not short-term, spatial memory. These results suggest that a caspase-mediated cellular event(s) in hippocampal neurons is critical for long-term spatial memory storage.

Long-Term Potentiation and Memory

Abstract: Lynch, MA. Long-Term Potentiation and Memory. Physiol Rev 84: 87–136, 2004; 10.1152/physrev.00014.2003.—One of the most significant challenges in neuroscience is to identify the cellular and molecu...

MAPK cascade signalling and synaptic plasticity

Abstract: The mitogen-activated protein kinase (MAPK) cascade that leads to the activation of extracellular signal-regulated kinases-1 and -2 (ERK1 and ERK2) has a key role in the differentiation of some cell types and the proliferation of others. However, several recent reports implicate this cascade in the control of synaptic plasticity in the adult brain. ERK signalling seems to be essential for characterized neuronal transcriptional events, and might also regulate synaptic targets to control plasticity. Another recently emerging story is the involvement of a 'parallel' but distinct kinase cascade leading to the activation of p38 MAPK, which might control distinct forms of synaptic plasticity.

Mechanisms of fear extinction

Abstract: Excessive fear and anxiety are hallmarks of a variety of disabling anxiety disorders that affect millions of people throughout the world. Hence, a greater understanding of the brain mechanisms involved in the inhibition of fear and anxiety is attracting increasing interest in the research community. In the laboratory, fear inhibition most often is studied through a procedure in which a previously fear conditioned organism is exposed to a fear-eliciting cue in the absence of any aversive event. This procedure results in a decline in conditioned fear responses that is attributed to a process called fear extinction. Extensive empirical work by behavioral psychologists has revealed basic behavioral characteristics of extinction, and theoretical accounts have emphasized extinction as a form of inhibitory learning as opposed to an erasure of acquired fear. Guided by this work, neuroscientists have begun to dissect the neural mechanisms involved, including the regions in which extinction-related plasticity occurs and the cellular and molecular processes that are engaged. The present paper will cover behavioral, theoretical and neurobiological work, and will conclude with a discussion of clinical implications.