bp(GO:learning)

Entity

Name

learning

Namespace

go

Namespace Version

20180921

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/go-names.belns

Significant transcriptional alterations were also associated with excitatory synaptic remodelling and plasticity, hippocampal neuronal transmission, learning and memory and ageing-related cognitive decline (Extended Data Fig. 5q, r) PubMed:30046111

In vivo studies have also shown that sAPP-alpha promotes learning and memory in animal models (Meziane et al. 1998; Taylor et al. 2008) PubMed:22122372

APP and APP/presenilin-1 (PS-1) mice do not show neurodegeneration (Irizarry et al., 1997) and yet show several features of AD, including accumulation of plaques and defects in learning (Hsiao et al., 1996), suggesting that many features of AD are not the result of neuronal loss. These animals nonetheless have swollen cholinergic nerve terminals at 12 months, suggesting defective nerve sprouting (Hernandez et al., 2001). PubMed:19293145

In addition, xanomeline produced statistically significant improvements in verbal learning and short-term memory, indicating efficacy in treating cognitive symptoms.40 Unfortunately, gastrointestinal side effects were observed, and dose limitations have removed it from consideration for long-term clinical use. PubMed:24511233

In brain slice electrophysiology studies, BQCA enhanced excitatory postsynaptic currents in medial prefrontal cortical neurons,69 an area critical for higher cognitive, learning, and memory functions.70 In pre-clinical animal studies, BQCA reversed scopolamine-impaired contextual fear conditioning and rescued medial prefrontal cortex-dependent discrimination reversal learning deficits in a transgenic mouse model of AD. PubMed:24511233

The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233

M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233

In brain slice electrophysiology studies, BQCA enhanced excitatory postsynaptic currents in medial prefrontal cortical neurons,69 an area critical for higher cognitive, learning, and memory functions.70 In pre-clinical animal studies, BQCA reversed scopolamine-impaired contextual fear conditioning and rescued medial prefrontal cortex-dependent discrimination reversal learning deficits in a transgenic mouse model of AD. PubMed:24511233

The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233

M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233

M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233

Conversely, the most commonly associated symptoms of AD are cognitive in nature and include deficits in learning and memory. However, 50%–80% of AD patients display psychotic and behavioral disturbances that are correlated with poor social and functional outcomes PubMed:24511233

AD is the most commonly diagnosed form of dementia and currently affects approximately 35 million individuals worldwide.7 AD is a progressive neurodegenerative disease that is characterized by a host of cognitive deficits, including impairments in learning and memory. In addition to the well-documented cognitive impairments, AD patients also display behavioral disturbances, including anxiety, depression, and psychosis PubMed:24511233

In animal studies, acute and chronic nicotine administration improves working memory, and nicotinic agonists were found to improve learning and memory in humans and nonhuman primates (145). PubMed:17009926

By modulating activity-dependent events, nAChRs participate in fundamental aspects of synaptic plasticity that are involved in attention, learning, memory, and development (3, 12–16). PubMed:17009926

It has been demonstrated that the role of ACh in learning and memory seems to be related to the regulation of glutamatergic neurotransmission PubMed:26813123

The cholinergic system is involved in critical physiological processes, such as attention, learning, memory, stress response, wakefulness and sleep, and sensory information PubMed:26813123

It has been demonstrated that the cholinergic system plays a role in the learning process PubMed:26813123

Chronic treatment with AF267B reduces Abeta plaques and tau hyperphosphorylation and rescues learning and memory impairments in 3×Tg AD mice PubMed:24590577

After brucine, several other M1-PAMs have been discovered, including VU0029767, VU0090157, and benzyl quinolone carboxylic acid (BQCA)[115-117]. These compounds do not activate M1 mAChR directly but greatly increase the affi nity of ACh for the M1 subtype. In addition, BQCA is effective in restoring discrimination reversal learning in a mouse model of AD and regulating nonamyloidogenic APP processing[117]. PubMed:24590577

Moreover, VU0184670 potentiates neuronal NMDAR-mediated currents in hippocampal brain slices and VU0357017 reverses the cognitive deficits induced by an mAChR antagonist in a contextual fear conditioning paradigm, exhibiting improvement of hippocampus-dependent learning[110, 123]. PubMed:24590577

Among the mAChR family members, the M1 subtype makes up 50–60% of the total and is predominantly expressed in all major areas of the forebrain, including the hippocampus, cerebral cortex, corpus striatum, and thalamus[36-38]. M1 mAChR-knockout mice show a series of cognitive defi cits and impairments in long-term potentiation, indicating that the M1 subtype is physiologically linked to multiple functions such as synaptic plasticity, neuronal excitability, neuronal differentiation during early development, and learning and memory PubMed:24590577

In the Morris water maze, NACHO knockout mice were delayed in learning the task during acquisition days 1–4 and showed fewer target crossings in the probe test (Figures S2Cand S2D), despite showing no significant difference for genotype on average speed through each acquisition day (ANOVA: F[1,28] = 0.004; p = 0.9492; data not shown) PubMed:28445721

In 2011, we know that cholinergic actions in the brain govern various processes: cognition (attention and executive function) (Couey et al., 2007; Levin and Rezvani, 2007; Heath and Picciotto, 2009; Howe et al., 2010), learning and memory (Gould, 2006; Couey et al., 2007; Levin and Rezvani, 2007), mood (anxiety, depression) (Picciotto et al., 2008), reward (addiction, craving) (Tang and Dani, 2009), and sensory processing (Heath and Picciotto, 2009) PubMed:21482353

As a consequence of nAChR hypersensitivity, lynx1 knockout mice display increased levels of Ca2+ in neurons, enhancements in synaptic efficacy, and improved learning and memory functions (Miwa et al., 2006; Darvas et al., 2009; Tekinay et al., 2009) PubMed:21482353

Acute administration of nicotine to AD patients has resulted in a measurable short-term improvement in learning, memory, and attentional performance (Jones et al 1992) PubMed:11230871

Moreover in Ab-received mice, treatment with PHA and Gal improved the acquisition performance on comparing with the normal saline group (p<0.001) PubMed:25881725

Moreover in Ab-received mice, treatment with PHA and Gal improved the acquisition performance on comparing with the normal saline group (p<0.001) PubMed:25881725

Notably, PHA could completely block the Ab-impaired task acquisition and reduce escape-latency to the normal level. Furthermore, the effect of PHA against the Ab-impaired task acquisition could be abolished by the pre-treatment of the a7 nAChR antagonist MLA (p<0.001). It was also noted that blockade of a7 nAChR by MLA in the Gal-treated group resulted in a significant prolongation of the escape-latency on comparing with the Gal group (p<0.001) (Fig. 2). PubMed:25881725

Inter-group analysis showed that Ab increased escape latency in MWM in comparison with normal saline and sham groups (p<0.001). In addition, sham operation did not have a significant effect on escape latency in comparison with the normal saline group (p>0.05). PubMed:25881725

Notably, PHA could completely block the Ab-impaired task acquisition and reduce escape-latency to the normal level. Furthermore, the effect of PHA against the Ab-impaired task acquisition could be abolished by the pre-treatment of the a7 nAChR antagonist MLA (p<0.001). It was also noted that blockade of a7 nAChR by MLA in the Gal-treated group resulted in a significant prolongation of the escape-latency on comparing with the Gal group (p<0.001) (Fig. 2). PubMed:25881725

As expected, AR-R17779 — a selective partial alpha7 nAChR agonist — improved scopolamine-elicited deficits in social recognition, and the 24-hour memory retention interval in unimpaired animals. Repeated doses of AR-R17779 enhanced long-term learning and attenuated working-memory deficits in rats. PubMed:19721446

First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446

These results clearly indicated that MPT0G211 can penetrate the BBB, where it potentially ameliorates learning and memory deficits. PubMed:29844403

Nuclear factor erythroid-2-related factor 2 (Nrf2) is a transcription factor known to increase the level of many antioxidants, including glutathione-S transferase (GST), and is negatively regulated by the activity of GSK-3β. Our results indicated the increased nuclear localization of Nrf2 and level of GST, suggesting the increased activity of the transcription factor as a result of GSK-3β suppression, consistent with the decreased oxidative stress observed. Consistent with the improved learning and memory, and consistent with GSK-3b being a tau kinase, we observed decreased tau phosphorylation in brain of GAO-treated SAMP8 mice compared to that of RAO-treated SAMP8 mice. PubMed:24355211

SIRT1 activation or elevation ameliorates pathology and neurodegeneration in AD (Qin et al., 2006; Kim et al., 2007). Loss of SIRT1 induces impairment of learning and memory (Gao et al., 2010; Michán et al., 2010). PubMed:29540553

Overexpression of TTBK1 was sufficient in inducing spatial learning impairment in mice, which is associated with enhanced Cdk5 activity and reduction in cell surface level of NR2B. Over-expressionof TTBK1 transgene in JNPL3 mice resulted in accumulation of pre-tangle forms of tau. Inaddition, TTBK1 expression plays a unique role in accelerating motor neuron degeneration and neuroinflammation in JNPL3mice. PubMed:24808823

Overexpression of TTBK1 was sufficient in inducing spatial learning impairment in mice, which is associated with enhanced Cdk5 activity and reduction in cell surface level of NR2B. Over-expressionof TTBK1 transgene in JNPL3 mice resulted in accumulation of pre-tangle forms of tau. Inaddition, TTBK1 expression plays a unique role in accelerating motor neuron degeneration and neuroinflammation in JNPL3mice. PubMed:24808823

In 25-month-old mice, the number of errors and the latency in the learning phase negatively correlated with the Sumo3 level in the dorsal hippocampus. PubMed:21843595

Overexpression of TTBK1 was sufficient in inducing spatial learning impairment in mice, which is associated with enhanced Cdk5 activity and reduction in cell surface level of NR2B. Over-expressionof TTBK1 transgene in JNPL3 mice resulted in accumulation of pre-tangle forms of tau. Inaddition, TTBK1 expression plays a unique role in accelerating motor neuron degeneration and neuroinflammation in JNPL3mice. PubMed:24808823

Probenecid has also been demonstrated to reduce the activation of the NLRP1 inflammasome, and improve the learning performance in age-related cognitive decline (Mawhinney et al., 2011) PubMed:24561250

Neurons from these animals exhibited increased oxidative stress, increased generation of ROS, DNA fragmentation, neuronal apoptosis, and impairment in learning, compared to single-transgenic mAPP mice. PubMed:30444369

Further experiments based on the injection of a PP2A inhibitor in the rat hippocampus demon- strated tau hyper-phosphorylation, and learning and memory deficits [49, 50]. PubMed:22299660

Soluble Ab oligomers inhibit hippocampal long-term potentiation and alter memory and learning performance PubMed:22908190

Stimulating lysosomal proteolytic efficiency in the TgCRND8 APP mouse model by deleting an endogenous inhibitor of lysosomal cysteine proteases (cystatin B) rescues lysosomal pathology, eliminates abnormal autolysosomal accumulation of autophagy substrates, including Ab, decreases Ab and amyloid deposition, and ameliorates learning and memory deficits (Yang et al. 2011) PubMed:22908190

The UPS is also critically involved in learning and memory. PubMed:22908190

Although key to the survival of all cells, endocytosis supports unique neuronal functions, including aspects of synaptic transmission and plasticity underlying memory and learning. PubMed:22908190

The molecular mechanisms underlying the aforementioned involvement of NF-κB proteins in learning and memory have not been completely comprehended, although recent evidence has implicated NF-κB – induced transcriptional activation of Protein Kinase A (PKA) catalytic subunit that culminates in activation of CREB (cyclic AMP-response element binding protein) signaling [77] which is regarded as the molecular switch that converts short-term memory to long-term memory PubMed:28745240

p50 knock-out mice exhibit severe deficits in learning as assessed by an active avoidance assay [93] in addition to displaying lack of anxiety-like behavior in well-established tests and paradigms that assess exploratory drive as a measure of anxiety PubMed:28745240

Ginsenoside Rd showed neuro-protective effects with A 40 activated impairments in rat brains [225] and ameliorated learning and memory capability in APP transgenic mice, via reducing the activity of NF-B [226]. PubMed:29179999

We evaluated the 31 transcripts regulated at both tested ages (see above) and found that the most enriched modified functions were related to nervous system development and activity including synapse assembly, positive regulation of synaptic transmission, glutamatergic, regulation of synapse organization, regulation of cell communication, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor clustering, learning or memory, social behavior, regulation of ion transport, vocalization behavior, and nervous system development (Figure 3, Supplemental Tables 11 and 12) PubMed:30106381

We evaluated the 31 transcripts regulated at both tested ages (see above) and found that the most enriched modified functions were related to nervous system development and activity including synapse assembly, positive regulation of synaptic transmission, glutamatergic, regulation of synapse organization, regulation of cell communication, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor clustering, learning or memory, social behavior, regulation of ion transport, vocalization behavior, and nervous system development (Figure 3, Supplemental Tables 11 and 12) PubMed:30106381

APP and APP/presenilin-1 (PS-1) mice do not show neurodegeneration (Irizarry et al., 1997) and yet show several features of AD, including accumulation of plaques and defects in learning (Hsiao et al., 1996), suggesting that many features of AD are not the result of neuronal loss. These animals nonetheless have swollen cholinergic nerve terminals at 12 months, suggesting defective nerve sprouting (Hernandez et al., 2001). PubMed:19293145

Conversely, the most commonly associated symptoms of AD are cognitive in nature and include deficits in learning and memory. However, 50%–80% of AD patients display psychotic and behavioral disturbances that are correlated with poor social and functional outcomes PubMed:24511233

The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233

M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233

The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233

M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233

M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233

In brain slice electrophysiology studies, BQCA enhanced excitatory postsynaptic currents in medial prefrontal cortical neurons,69 an area critical for higher cognitive, learning, and memory functions.70 In pre-clinical animal studies, BQCA reversed scopolamine-impaired contextual fear conditioning and rescued medial prefrontal cortex-dependent discrimination reversal learning deficits in a transgenic mouse model of AD. PubMed:24511233

By modulating activity-dependent events, nAChRs participate in fundamental aspects of synaptic plasticity that are involved in attention, learning, memory, and development (3, 12–16). PubMed:17009926

The cholinergic system is involved in critical physiological processes, such as attention, learning, memory, stress response, wakefulness and sleep, and sensory information PubMed:26813123

It has been demonstrated that the cholinergic system plays a role in the learning process PubMed:26813123

It has been demonstrated that the role of ACh in learning and memory seems to be related to the regulation of glutamatergic neurotransmission PubMed:26813123

Among the mAChR family members, the M1 subtype makes up 50–60% of the total and is predominantly expressed in all major areas of the forebrain, including the hippocampus, cerebral cortex, corpus striatum, and thalamus[36-38]. M1 mAChR-knockout mice show a series of cognitive defi cits and impairments in long-term potentiation, indicating that the M1 subtype is physiologically linked to multiple functions such as synaptic plasticity, neuronal excitability, neuronal differentiation during early development, and learning and memory PubMed:24590577

In 2011, we know that cholinergic actions in the brain govern various processes: cognition (attention and executive function) (Couey et al., 2007; Levin and Rezvani, 2007; Heath and Picciotto, 2009; Howe et al., 2010), learning and memory (Gould, 2006; Couey et al., 2007; Levin and Rezvani, 2007), mood (anxiety, depression) (Picciotto et al., 2008), reward (addiction, craving) (Tang and Dani, 2009), and sensory processing (Heath and Picciotto, 2009) PubMed:21482353

First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446

Overexpression of TTBK1 was sufficient in inducing spatial learning impairment in mice, which is associated with enhanced Cdk5 activity and reduction in cell surface level of NR2B. Over-expressionof TTBK1 transgene in JNPL3 mice resulted in accumulation of pre-tangle forms of tau. Inaddition, TTBK1 expression plays a unique role in accelerating motor neuron degeneration and neuroinflammation in JNPL3mice. PubMed:24808823

Overexpression of TTBK1 was sufficient in inducing spatial learning impairment in mice, which is associated with enhanced Cdk5 activity and reduction in cell surface level of NR2B. Over-expressionof TTBK1 transgene in JNPL3 mice resulted in accumulation of pre-tangle forms of tau. Inaddition, TTBK1 expression plays a unique role in accelerating motor neuron degeneration and neuroinflammation in JNPL3mice. PubMed:24808823

Overexpression of TTBK1 was sufficient in inducing spatial learning impairment in mice, which is associated with enhanced Cdk5 activity and reduction in cell surface level of NR2B. Over-expressionof TTBK1 transgene in JNPL3 mice resulted in accumulation of pre-tangle forms of tau. Inaddition, TTBK1 expression plays a unique role in accelerating motor neuron degeneration and neuroinflammation in JNPL3mice. PubMed:24808823

Nuclear factor erythroid-2-related factor 2 (Nrf2) is a transcription factor known to increase the level of many antioxidants, including glutathione-S transferase (GST), and is negatively regulated by the activity of GSK-3β. Our results indicated the increased nuclear localization of Nrf2 and level of GST, suggesting the increased activity of the transcription factor as a result of GSK-3β suppression, consistent with the decreased oxidative stress observed. Consistent with the improved learning and memory, and consistent with GSK-3b being a tau kinase, we observed decreased tau phosphorylation in brain of GAO-treated SAMP8 mice compared to that of RAO-treated SAMP8 mice. PubMed:24355211

SIRT1 activation or elevation ameliorates pathology and neurodegeneration in AD (Qin et al., 2006; Kim et al., 2007). Loss of SIRT1 induces impairment of learning and memory (Gao et al., 2010; Michán et al., 2010). PubMed:29540553

In 25-month-old mice, the number of errors and the latency in the learning phase negatively correlated with the Sumo3 level in the dorsal hippocampus. PubMed:21843595

The UPS is also critically involved in learning and memory. PubMed:22908190

We evaluated the 31 transcripts regulated at both tested ages (see above) and found that the most enriched modified functions were related to nervous system development and activity including synapse assembly, positive regulation of synaptic transmission, glutamatergic, regulation of synapse organization, regulation of cell communication, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor clustering, learning or memory, social behavior, regulation of ion transport, vocalization behavior, and nervous system development (Figure 3, Supplemental Tables 11 and 12) PubMed:30106381

We evaluated the 31 transcripts regulated at both tested ages (see above) and found that the most enriched modified functions were related to nervous system development and activity including synapse assembly, positive regulation of synaptic transmission, glutamatergic, regulation of synapse organization, regulation of cell communication, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor clustering, learning or memory, social behavior, regulation of ion transport, vocalization behavior, and nervous system development (Figure 3, Supplemental Tables 11 and 12) PubMed:30106381