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In search of a recognition memory engram.

Brown MW, Banks PJ - Neurosci Biobehav Rev (2014)

Bottom Line: Familiarity discrimination for individual visual stimuli seems to be effected by a system centred on the perirhinal cortex of the temporal lobe.The fundamental change that encodes prior occurrence within the perirhinal cortex is a reduction in the responses of neurones when a stimulus is repeated.A review is given of findings indicating that perirhinal cortex acts as a storage site for recognition memory of objects and that such storage depends upon processes producing synaptic weakening.

View Article: PubMed Central - PubMed

Affiliation: University of Bristol, School of Physiology and Pharmacology, Medical Sciences Building, Bristol BS8 1TD, UK. Electronic address: M.W.Brown@Bristol.ac.uk.

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LTD pathways in perirhinal cortex. (1) Activation of glutamatergic and cholinergic afferents in perirhinal cortex, typically at 1–5 Hz, leads to release of neurotransmitter and activation of post-synaptic receptors. (2) Kainate receptor (KAR) activation is required for familiarity discrimination at short (≤20 min) but not longer delays. Although there are no currently known roles for kainate receptors in perirhinal plasticity, it is known that inhibition of AP2-dependent AMPA receptor endocytosis by pepD849-Q853 also impairs object recognition memory at short delays, thus suggesting that KARs are also involved in synaptic weakening processes. (3) Cholinergic modulation of perirhinal cortex is implicated in both learning and protein synthesis-dependent LTD. Muscarinic acetylcholine receptor 1 (mAChR1) activation leads to release of calcium from intracellular stores and subsequent activation of calcium-sensitive kinases, and additionally stimulates extracellular-signal related kinases (ERK) leading to phosphorylation of CREB and production of Fos protein. Muscarinic receptor activation also activates nitric oxide synthase (NOS), producing nitric oxide (NO) which can act as a retrograde signalling molecule, activating soluble guanylate cyclase which attenuates glutamate release. Block of mAChR1s during acquisition impairs object recognition memory at delays of up to 6 h, whilst inhibition of NOS impairs memory at a delay of 24 h, suggesting mechanisms other than mAChR1 may also stimulate NO production in perirhinal cortex. (4) Activation of L-type voltage gated calcium channels (VGCCs), mGluRs and GluN2B-containing NMDA receptors are all required for object recognition at a 24 h delay. Activation of these proteins leads to increases in intracellular calcium concentration and calcium–calmodulin dependent kinase (CamK) activation which is thought to phosphorylate AMPA receptors and facilitate their endocytosis. (5) CREB phosphorylation is required for object recognition memory at a 24 h delay and is increased by mGluR, mAChR1 and calcium–calmodulin dependent kinase (CamK) activation. Phosphorylated CREB stimulates transcription and is known to lead to production of Fos protein. Although these events are required for object recognition memory and LTD, it is currently unclear how these processes lead to synaptic weakening. It is however known that endocytosis of AMPA receptors by clathrin adaptor protein AP2 is required for both LTD and object recognition memory at delays of 5 min or 24 h.
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fig0030: LTD pathways in perirhinal cortex. (1) Activation of glutamatergic and cholinergic afferents in perirhinal cortex, typically at 1–5 Hz, leads to release of neurotransmitter and activation of post-synaptic receptors. (2) Kainate receptor (KAR) activation is required for familiarity discrimination at short (≤20 min) but not longer delays. Although there are no currently known roles for kainate receptors in perirhinal plasticity, it is known that inhibition of AP2-dependent AMPA receptor endocytosis by pepD849-Q853 also impairs object recognition memory at short delays, thus suggesting that KARs are also involved in synaptic weakening processes. (3) Cholinergic modulation of perirhinal cortex is implicated in both learning and protein synthesis-dependent LTD. Muscarinic acetylcholine receptor 1 (mAChR1) activation leads to release of calcium from intracellular stores and subsequent activation of calcium-sensitive kinases, and additionally stimulates extracellular-signal related kinases (ERK) leading to phosphorylation of CREB and production of Fos protein. Muscarinic receptor activation also activates nitric oxide synthase (NOS), producing nitric oxide (NO) which can act as a retrograde signalling molecule, activating soluble guanylate cyclase which attenuates glutamate release. Block of mAChR1s during acquisition impairs object recognition memory at delays of up to 6 h, whilst inhibition of NOS impairs memory at a delay of 24 h, suggesting mechanisms other than mAChR1 may also stimulate NO production in perirhinal cortex. (4) Activation of L-type voltage gated calcium channels (VGCCs), mGluRs and GluN2B-containing NMDA receptors are all required for object recognition at a 24 h delay. Activation of these proteins leads to increases in intracellular calcium concentration and calcium–calmodulin dependent kinase (CamK) activation which is thought to phosphorylate AMPA receptors and facilitate their endocytosis. (5) CREB phosphorylation is required for object recognition memory at a 24 h delay and is increased by mGluR, mAChR1 and calcium–calmodulin dependent kinase (CamK) activation. Phosphorylated CREB stimulates transcription and is known to lead to production of Fos protein. Although these events are required for object recognition memory and LTD, it is currently unclear how these processes lead to synaptic weakening. It is however known that endocytosis of AMPA receptors by clathrin adaptor protein AP2 is required for both LTD and object recognition memory at delays of 5 min or 24 h.

Mentions: As synaptic changes are hypothesised to be involved in the encoding of memory, and response changes have been recorded in perirhinal cortex in response to learning, it follows that pharmacological manipulations which impair memory should also impair synaptic plasticity if such plasticity mechanisms are responsible for memory storage. This relationship has been investigated using electrophysiological recordings of in vitro brain slice preparations. Synaptic enhancement (long-term potentiation: LTP) and synaptic weakening (long-term depression: LTD) can be produced in perirhinal cortical slices by appropriately patterned electrical stimulation (Liu and Bilkey, 1996; Ziakopoulos et al., 1999) (Fig. 6). For the most part those compounds which impair recognition memory have also been found to block induction or expression of synaptic plasticity in vitro, supporting the hypothesis that synaptic plasticity underlies recognition memory and informing us to some extent of the direction of plasticity affected by pharmacological intervention. However, one must be cautious not to use in vitro plasticity data as a proxy for recognition memory processes – the tone of afferent inputs to perirhinal cortical slices is significantly distorted. Furthermore, the stimulation patterns delivered to slices to induce activity-dependent synaptic plasticity are usually not consistent with those which occur in vivo, often stimulation lasting many seconds or minutes is applied to bring about synaptic changes which are thought to be expressed in a matter of milliseconds in behaving animals (Xiang and Brown, 1998), although exploration of novel object-place arrangements have been shown to affect induction of hippocampal plasticity in vivo using such protocols (Kemp and Manahan-Vaughan, 2004). Nevertheless, plasticity studies have proved useful tools in deciphering the molecular changes which may occur in the perirhinal cortex during object recognition memory formation. Electrophysiological studies of plasticity in chick IMM have similarly sought to make links to learning (e.g. Bradley et al., 1991a,b, 1992, 1999).


In search of a recognition memory engram.

Brown MW, Banks PJ - Neurosci Biobehav Rev (2014)

LTD pathways in perirhinal cortex. (1) Activation of glutamatergic and cholinergic afferents in perirhinal cortex, typically at 1–5 Hz, leads to release of neurotransmitter and activation of post-synaptic receptors. (2) Kainate receptor (KAR) activation is required for familiarity discrimination at short (≤20 min) but not longer delays. Although there are no currently known roles for kainate receptors in perirhinal plasticity, it is known that inhibition of AP2-dependent AMPA receptor endocytosis by pepD849-Q853 also impairs object recognition memory at short delays, thus suggesting that KARs are also involved in synaptic weakening processes. (3) Cholinergic modulation of perirhinal cortex is implicated in both learning and protein synthesis-dependent LTD. Muscarinic acetylcholine receptor 1 (mAChR1) activation leads to release of calcium from intracellular stores and subsequent activation of calcium-sensitive kinases, and additionally stimulates extracellular-signal related kinases (ERK) leading to phosphorylation of CREB and production of Fos protein. Muscarinic receptor activation also activates nitric oxide synthase (NOS), producing nitric oxide (NO) which can act as a retrograde signalling molecule, activating soluble guanylate cyclase which attenuates glutamate release. Block of mAChR1s during acquisition impairs object recognition memory at delays of up to 6 h, whilst inhibition of NOS impairs memory at a delay of 24 h, suggesting mechanisms other than mAChR1 may also stimulate NO production in perirhinal cortex. (4) Activation of L-type voltage gated calcium channels (VGCCs), mGluRs and GluN2B-containing NMDA receptors are all required for object recognition at a 24 h delay. Activation of these proteins leads to increases in intracellular calcium concentration and calcium–calmodulin dependent kinase (CamK) activation which is thought to phosphorylate AMPA receptors and facilitate their endocytosis. (5) CREB phosphorylation is required for object recognition memory at a 24 h delay and is increased by mGluR, mAChR1 and calcium–calmodulin dependent kinase (CamK) activation. Phosphorylated CREB stimulates transcription and is known to lead to production of Fos protein. Although these events are required for object recognition memory and LTD, it is currently unclear how these processes lead to synaptic weakening. It is however known that endocytosis of AMPA receptors by clathrin adaptor protein AP2 is required for both LTD and object recognition memory at delays of 5 min or 24 h.
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Related In: Results  -  Collection

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fig0030: LTD pathways in perirhinal cortex. (1) Activation of glutamatergic and cholinergic afferents in perirhinal cortex, typically at 1–5 Hz, leads to release of neurotransmitter and activation of post-synaptic receptors. (2) Kainate receptor (KAR) activation is required for familiarity discrimination at short (≤20 min) but not longer delays. Although there are no currently known roles for kainate receptors in perirhinal plasticity, it is known that inhibition of AP2-dependent AMPA receptor endocytosis by pepD849-Q853 also impairs object recognition memory at short delays, thus suggesting that KARs are also involved in synaptic weakening processes. (3) Cholinergic modulation of perirhinal cortex is implicated in both learning and protein synthesis-dependent LTD. Muscarinic acetylcholine receptor 1 (mAChR1) activation leads to release of calcium from intracellular stores and subsequent activation of calcium-sensitive kinases, and additionally stimulates extracellular-signal related kinases (ERK) leading to phosphorylation of CREB and production of Fos protein. Muscarinic receptor activation also activates nitric oxide synthase (NOS), producing nitric oxide (NO) which can act as a retrograde signalling molecule, activating soluble guanylate cyclase which attenuates glutamate release. Block of mAChR1s during acquisition impairs object recognition memory at delays of up to 6 h, whilst inhibition of NOS impairs memory at a delay of 24 h, suggesting mechanisms other than mAChR1 may also stimulate NO production in perirhinal cortex. (4) Activation of L-type voltage gated calcium channels (VGCCs), mGluRs and GluN2B-containing NMDA receptors are all required for object recognition at a 24 h delay. Activation of these proteins leads to increases in intracellular calcium concentration and calcium–calmodulin dependent kinase (CamK) activation which is thought to phosphorylate AMPA receptors and facilitate their endocytosis. (5) CREB phosphorylation is required for object recognition memory at a 24 h delay and is increased by mGluR, mAChR1 and calcium–calmodulin dependent kinase (CamK) activation. Phosphorylated CREB stimulates transcription and is known to lead to production of Fos protein. Although these events are required for object recognition memory and LTD, it is currently unclear how these processes lead to synaptic weakening. It is however known that endocytosis of AMPA receptors by clathrin adaptor protein AP2 is required for both LTD and object recognition memory at delays of 5 min or 24 h.
Mentions: As synaptic changes are hypothesised to be involved in the encoding of memory, and response changes have been recorded in perirhinal cortex in response to learning, it follows that pharmacological manipulations which impair memory should also impair synaptic plasticity if such plasticity mechanisms are responsible for memory storage. This relationship has been investigated using electrophysiological recordings of in vitro brain slice preparations. Synaptic enhancement (long-term potentiation: LTP) and synaptic weakening (long-term depression: LTD) can be produced in perirhinal cortical slices by appropriately patterned electrical stimulation (Liu and Bilkey, 1996; Ziakopoulos et al., 1999) (Fig. 6). For the most part those compounds which impair recognition memory have also been found to block induction or expression of synaptic plasticity in vitro, supporting the hypothesis that synaptic plasticity underlies recognition memory and informing us to some extent of the direction of plasticity affected by pharmacological intervention. However, one must be cautious not to use in vitro plasticity data as a proxy for recognition memory processes – the tone of afferent inputs to perirhinal cortical slices is significantly distorted. Furthermore, the stimulation patterns delivered to slices to induce activity-dependent synaptic plasticity are usually not consistent with those which occur in vivo, often stimulation lasting many seconds or minutes is applied to bring about synaptic changes which are thought to be expressed in a matter of milliseconds in behaving animals (Xiang and Brown, 1998), although exploration of novel object-place arrangements have been shown to affect induction of hippocampal plasticity in vivo using such protocols (Kemp and Manahan-Vaughan, 2004). Nevertheless, plasticity studies have proved useful tools in deciphering the molecular changes which may occur in the perirhinal cortex during object recognition memory formation. Electrophysiological studies of plasticity in chick IMM have similarly sought to make links to learning (e.g. Bradley et al., 1991a,b, 1992, 1999).

Bottom Line: Familiarity discrimination for individual visual stimuli seems to be effected by a system centred on the perirhinal cortex of the temporal lobe.The fundamental change that encodes prior occurrence within the perirhinal cortex is a reduction in the responses of neurones when a stimulus is repeated.A review is given of findings indicating that perirhinal cortex acts as a storage site for recognition memory of objects and that such storage depends upon processes producing synaptic weakening.

View Article: PubMed Central - PubMed

Affiliation: University of Bristol, School of Physiology and Pharmacology, Medical Sciences Building, Bristol BS8 1TD, UK. Electronic address: M.W.Brown@Bristol.ac.uk.

Show MeSH