Multi-level analyses of associative recognition memory: the whole is greater than the sum of its parts.

Associative recognition memory depends on the integration of information concerning an item and the spatio-temporal context in which it was encountered. Such an integration depends on dynamic interactions across a brain-wide memory network. Here we discuss evidence from multiple levels of analysis, behavioural, cellular and synaptic which demonstrating the existence of multiple overlapping, subnetworks embedded within these large-scale networks.

CREB transcription in the medial prefrontal cortex regulates the formation of long-term associative recognition memory.

The medial prefrontal cortex (mPFC) is known to be critical for specific forms of long-term recognition memory, however the cellular mechanisms in the mPFC that underpin memory maintenance have not been well characterized. This study examined the importance of phosphorylation of cAMP responsive element binding protein (CREB) in the mPFC for different forms of long-term recognition memory in the rat. Adenoviral transduction of the mPFC with a dominant-negative inhibitor of CREB impaired object-in-place memory following a 6 or 24 h retention delay, but no impairment was observed following delays of 5 min or 3 h.

Contrasting roles for DNA methyltransferases and histone deacetylases in single-item and associative recognition memory.

Recognition memory enables us to judge whether we have encountered a stimulus before and to recall associated information, including where the stimulus was encountered. The perirhinal cortex (PRh) is required for judgment of stimulus familiarity, while hippocampus (HPC) and medial prefrontal cortex (mPFC) are additionally involved when spatial information associated with a stimulus needs to be remembered. While gene expression is known to be essential for the consolidation of long-term recognition memory, the underlying regulatory mechanisms are not fully understood.

Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory.

Unlabelled: Finding effective cognitive enhancers is a major health challenge; however, modulating glutamatergic neurotransmission has the potential to enhance performance in recognition memory tasks. Previous studies using glutamate receptor antagonists have revealed that the medial prefrontal cortex (mPFC) plays a central role in associative recognition memory. The present study investigates short-term recognition memory using optogenetics to target glutamatergic neurons within the rodent mPFC specifically.

Disruption of hippocampal-prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission.

Functional connectivity between the hippocampus and prefrontal cortex (PFC) is essential for associative recognition memory and working memory. Disruption of hippocampal-PFC synchrony occurs in schizophrenia, which is characterized by hypofunction of NMDA receptor (NMDAR)-mediated transmission. We demonstrate that activity of dopamine D2-like receptors (D2Rs) leads selectively to long-term depression (LTD) of hippocampal-PFC NMDAR-mediated synaptic transmission.

Early memory formation disrupted by atypical PKC inhibitor ZIP in the medial prefrontal cortex but not hippocampus.

Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesized to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluA2 subunit. A myristoylated PKMζ pseudosubstrate peptide (ZIP) blocks PKMζ activity. We examined the actions of ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition memory in rats during early memory formation and memory maintenance.

Object-in-place associative recognition memory depends on glutamate receptor neurotransmission within two defined hippocampal-cortical circuits: a critical role for AMPA and NMDA receptors in the hippocampus, perirhinal, and prefrontal cortices.

Object-in-place associative recognition memory depends on an interaction between the hippocampus (HPC), perirhinal (PRH), and medial prefrontal (mPFC) cortices, yet the contribution of glutamate receptor neurotransmission to these interactions is unknown. NMDA receptors (NMDAR) in the HPC were critical for encoding of object-in-place memory but not for single-item object recognition. Next, a disconnection procedure was used to examine the importance of "concurrent" glutamate neurotransmission in the HPC-mPFC and HPC-PRH.

Investigations into the involvement of NMDA mechanisms in recognition memory.

This review will focus on evidence showing that NMDA receptor neurotransmission is critical for synaptic plasticity processes within brain regions known to be necessary for the formation of object recognition memories. The aim will be to provide evidence concerning NMDA mechanisms related to recognition memory processes and show that recognition memory for objects, places or associations between objects and places depends on NMDA neurotransmission within the perirhinal cortex, temporal association cortex medial prefrontal cortex and hippocampus. Administration of the NMDA antagonist AP5, selectively into each of these brain regions has revealed that the extent of the involvement NMDA receptors appears dependent on the type of information required to solve the recognition memory task; thus NMDA receptors in the perirhinal cortex are crucial for the encoding of long-term recognition memory for objects, and object-in-place associations, but not for short-term recognition memory or for retrieval.

When is the hippocampus involved in recognition memory?

The role of the hippocampus in recognition memory is controversial. Recognition memory judgments may be made using different types of information, including object familiarity, an object's spatial location, or when an object was encountered. Experiment 1 examined the role of the hippocampus in recognition memory tasks that required the animals to use these different types of mnemonic information.

Study of novel selective mGlu2 agonist in the temporo-ammonic input to CA1 neurons reveals reduced mGlu2 receptor expression in a Wistar substrain with an anxiety-like phenotype.

Group II metabotropic receptors (mGluRs) regulate central synaptic transmission by modulating neurotransmitter release. However, the lack of pharmacological tools differentiating between mGlu2 and mGlu3 receptors has hampered identification of the roles of these two receptor subtypes. We have used LY395756 [(1SR,2SR,4RS,5RS,6SR)-2-amino-4-methylbicyclo[3.

Critical role of the cholinergic system for object-in-place associative recognition memory.

Object-in-place memory, which relies on the formation of associations between an object and the place in which it was encountered, depends upon a neural circuit comprising the perirhinal (PRH) and medial prefrontal (mPFC) cortices. This study examined the contribution of muscarinic cholinergic neurotransmission within this circuit to such object-in-place associative memory. Intracerebral administration of scopolamine in the PRH or mPFC impaired memory acquisition, but not retrieval and importantly we showed that unilateral blockade of muscarinic receptors simultaneously in both regions in opposite hemispheres, significantly impaired performance.

NMDA receptor plasticity in the perirhinal and prefrontal cortices is crucial for the acquisition of long-term object-in-place associative memory.

A key process for recognition memory is the formation of associations between an object and the place in which it was encountered, a process that has been shown to require the perirhinal (PRH) and medial prefrontal (mPFC) cortices. Here we demonstrate, for the first time, the importance of glutamatergic neurotransmission, within the PRH and mPFC, for object-in-place associative recognition memory. Unilateral blockade of AMPA receptors (by CNQX) in the PRH and mPFC in opposite hemispheres impaired an object-in-place task in rats, confirming that these cortical regions operate within a neural network for object-in-place recognition memory.

Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex.

Recognition memory requires judgments of the previous occurrence of stimuli made on the basis of the relative familiarity of individual objects, or by integrating information concerning objects and location, or by using recency information. The present study examined the role of the medial prefrontal cortex (mPFC) and perirhinal cortex (PRH) in these distinct recognition memory processes using a series of behavioral tests: a novel object preference task, an object-in-place task, and a temporal order memory task. Also, a disconnection procedure was used to test whether these regions form components of an integrated system for recognition memory.

A temporally distinct role for group I and group II metabotropic glutamate receptors in object recognition memory.

Recognition memory, involving the ability to discriminate between a novel and familiar object, depends on the integrity of the perirhinal cortex (PRH). Glutamate, the main excitatory neurotransmitter in the cortex, is essential for many types of memory processes. Of the subtypes of glutamate receptor, metabotropic receptors (mGluRs) have received less study than NMDA receptors; thus, the reported experiments examined the role of mGluRs in familiarity discrimination in the rat PRH.

The different effects on recognition memory of perirhinal kainate and NMDA glutamate receptor antagonism: implications for underlying plasticity mechanisms.

To investigate the involvement of different types of glutamate receptors in recognition memory, selective antagonists of NMDA and kainate receptors were locally infused into the perirhinal cortex of the rat temporal lobe. Such infusion of a selective kainate receptor antagonist produced an unusual pattern of recognition memory impairment: amnesia after a short (20 min) but not a long (24 h) delay. In contrast, antagonism of perirhinal NMDA glutamate receptors by locally infused AP-5 (2-amino-5-phosphonopentanoic acid) impaired recognition memory after the long but not the short delay.

Cholinergic neurotransmission is essential for perirhinal cortical plasticity and recognition memory.

We establish the importance of cholinergic neurotransmission to both recognition memory and plasticity within the perirhinal cortex of the temporal lobe. The muscarinic receptor antagonist scopolamine impaired the preferential exploration of novel over familiar objects, disrupted the normal reduced activation of perirhinal neurones to familiar compared to novel pictures, and blocked production of long-term depression (LTD) but not long-term potentiation (LTP) of synaptic transmission in perirhinal slices. The consistency of these effects across the behavioral, systems, and cellular levels of analysis provides strong evidence for the involvement of cholinergic mechanisms in synaptic plastic processes within perirhinal cortex that are necessary for recognition memory.