Toward an integrative perspective on hippocampal function: from the rapid encoding of experience to adaptive behavior.

The mammalian hippocampus has been associated with learning and memory, as well as with many other behavioral processes. In this article, these different perspectives are brought together, and it is pointed out that integration of diverse functional domains may be a key feature enabling the hippocampus to support not only the encoding and retrieval of certain memory representations, but also their translation into adaptive behavior. The hippocampus appears to combine: (i) sensory afferents and synaptic mechanisms underlying certain types of rapid learning; and (ii) links to motivational, emotional, executive, and sensorimotor functions.

Exploring the role of context-dependent hippocampal activity in spatial alternation behavior.

In a continuous T-maze spatial alternation task, CA1 place cells fire differentially on the stem of the maze as rats are performing left- and right-turn trials (Wood et al. (2000) Neuron 27:623-633). This context-dependent hippocampal activity provides a potential mechanism by which animals could solve the alternation task, as it provides a cue that could prime the appropriate goal choice.

Schemas and memory consolidation.

Memory encoding occurs rapidly, but the consolidation of memory in the neocortex has long been held to be a more gradual process. We now report, however, that systems consolidation can occur extremely quickly if an associative "schema" into which new information is incorporated has previously been created. In experiments using a hippocampal-dependent paired-associate task for rats, the memory of flavor-place associations became persistent over time as a putative neocortical schema gradually developed.

Active beta-amyloid immunization restores spatial learning in PDAPP mice displaying very low levels of beta-amyloid.

The behavioral and biochemical impact of active immunization against human beta-amyloid (Abeta) was assessed using male transgenic (Tg) mice overexpressing a human mutant amyloid precursor protein (heterozygous PDAPP mice) and littermate controls. Administration of aggregated Abeta42 occurred at monthly intervals from 7 months ("prevention") or 11 months ("reversal"), followed by double-blind behavioral training at 16 months on a cued task, then serial spatial learning in a water maze. Using a 2 x 2 design, with Abeta42 adjuvanted with MPL-AF (adjuvant formulation of monophosphoryl lipid A) or MPL-AF alone, PDAPP mice were impaired compared with non-Tg littermates on two separate measures of serial spatial learning.

The rodent hippocampus and spatial memory: from synapses to systems.

Although its operations are not limited to the spatial domain, there is a near consensus that the hippocampus plays a critical role in memory for place. This review aims to explore this role, with a particular emphasis on the functions performed by distinct hippocampal subregions. The use of innovative lesioning techniques, localized pharmacological treatments, and molecular genetic interventions is offering increasingly precise brain-regional specificity and temporal control.

Age effects on the neural correlates of episodic retrieval: increased cortical recruitment with matched performance.

Functional neuroimaging investigations have revealed a range of age-related differences in the neural correlates of episodic memory retrieval. Typically, whereas activity is reduced in older compared with younger adults in some regions, other regions are engaged exclusively, or to a greater extent, in older adults. It is unclear whether such differences merely represent the neural correlates of the lower levels of memory performance and impaired recollection typical of older adults.

Dopaminergic modulation of the persistence of one-trial hippocampus-dependent memory.

The persistence of new memory traces in the hippocampus, encoded following appropriate activation of glutamatergic receptors and the induction of synaptic plasticity, can be influenced by heterosynaptic activation of neuromodulatory brain systems. We therefore investigated the effects of a hippocampus-specific blockade of dopamine D1/D5 receptors on the persistence of spatial memory encoded in one trial using a delayed matching-to-place (DMP) task in a watermaze in which rats learn a new escape location each day. A within-subjects design was used such that both short (20 min) and long (6 h) retention intervals, and both drug (SCH23390, a D1/D5 receptor antagonist) and vehicle (aCSF) infusions were tested on different days in the same animals.

Elements of a neurobiological theory of hippocampal function: the role of synaptic plasticity, synaptic tagging and schemas.

The 2004 EJN Lecture was an attempt to lay out further aspects of a developing neurobiological theory of hippocampal function [Morris, R.G.M.

Memory reconsolidation: sensitivity of spatial memory to inhibition of protein synthesis in dorsal hippocampus during encoding and retrieval.

Reconsolidation is a putative neuronal process in which the retrieval of a previously consolidated memory returns it to a labile state that is once again subject to stabilization. This study explored the idea that reconsolidation occurs in spatial memory when animals retrieve memory under circumstances in which new memory encoding is likely to occur. Control studies confirmed that intrahippocampal infusions of anisomycin inhibited protein synthesis locally and that the spatial training protocols we used are subject to overnight protein synthesis-dependent consolidation.