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Article ; Online: NMDARs in prefrontal cortex - Regulation of synaptic transmission and plasticity.

Banks, Paul J / Bashir, Zafar I

2021 Volume 192, Page(s) 108614

Abstract: In this review we consider the various roles played by N-methyl-d-aspartate receptors (NMDARs) located on pyramidal neurones in medial prefrontal cortex (mPFC). We focus on recent data from our lab that has investigated how NMDARs contribute to ongoing ... ...

Abstract	In this review we consider the various roles played by N-methyl-d-aspartate receptors (NMDARs) located on pyramidal neurones in medial prefrontal cortex (mPFC). We focus on recent data from our lab that has investigated how NMDARs contribute to ongoing synaptic transmission in a frequency dependent manner, the plasticity of NMDARs and how this impacts their contribution to synaptic transmission, and finally consider how NMDARs contribute to plasticity induced by synchronous activation of two separate inputs to mPFC.
MeSH term(s)	Animals ; Humans ; Long-Term Potentiation/physiology ; Neuronal Plasticity/physiology ; Prefrontal Cortex/physiology ; Receptors, N-Methyl-D-Aspartate/physiology ; Synaptic Transmission/physiology
Chemical Substances	Receptors, N-Methyl-D-Aspartate
Language	English
Publishing date	2021-05-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2021.108614
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Article ; Online: Inhibiting cholinergic signalling in the cerebellar interpositus nucleus impairs motor behaviour.

Pickford, Jasmine / Iosif, Cristiana I / Bashir, Zafar I / Apps, Richard

The European journal of neuroscience

2023 Volume 59, Issue 9, Page(s) 2208–2224

Abstract: The role of neuromodulators in the cerebellum is not well understood. In particular, the behavioural significance of the cholinergic system in the cerebellum is unknown. To investigate the importance of cerebellar cholinergic signalling in behaviour, we ... ...

Abstract	The role of neuromodulators in the cerebellum is not well understood. In particular, the behavioural significance of the cholinergic system in the cerebellum is unknown. To investigate the importance of cerebellar cholinergic signalling in behaviour, we infused acetylcholine receptor antagonists, scopolamine and mecamylamine, bilaterally into the rat cerebellum (centred on interpositus nucleus) and observed the motor effects through a battery of behavioural tests. These tests included unrewarded behaviour during open field exploration and a horizontal ladder walking task and reward-based beam walking and pellet reaching tasks. Infusion of a mix of the antagonists did not impair motor learning in the horizontal ladder walking or the reaching task but reduced spontaneous movement during open field exploration, impaired coordination during beam walking and ladder walking, led to fewer reaches in the pellet reaching task, slowed goal-directed reaching behaviour and reduced reward pellet consumption in a free access to food task. Infusion of the muscarinic antagonist scopolamine on its own resulted in deficits in motor performance and a reduction in the number of reward pellets consumed in the free access to food task. By contrast, infusion of the nicotinic antagonist mecamylamine on its own had no significant effect on any task, except beam walking traversal time, which was reduced. Together, these data suggest that acetylcholine in the cerebellar interpositus nucleus is important for the execution and coordination of voluntary movements mainly via muscarinic receptor signalling, especially in relation to reward-related behaviour.
MeSH term(s)	Animals ; Scopolamine/pharmacology ; Mecamylamine/pharmacology ; Male ; Cerebellar Nuclei/physiology ; Cerebellar Nuclei/drug effects ; Rats ; Cholinergic Antagonists/pharmacology ; Motor Activity/drug effects ; Motor Activity/physiology ; Acetylcholine/metabolism ; Muscarinic Antagonists/pharmacology ; Nicotinic Antagonists/pharmacology ; Reward ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Rats, Long-Evans
Chemical Substances	Scopolamine (DL48G20X8X) ; Mecamylamine (6EE945D3OK) ; Cholinergic Antagonists ; Acetylcholine (N9YNS0M02X) ; Muscarinic Antagonists ; Nicotinic Antagonists
Language	English
Publishing date	2023-07-16
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/ejn.16066
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Article ; Online: Plasticity in Prefrontal Cortex Induced by Coordinated Synaptic Transmission Arising from Reuniens/Rhomboid Nuclei and Hippocampus.

Banks, Paul J / Warburton, E Clea / Bashir, Zafar I

Cerebral cortex communications

2021 Volume 2, Issue 2, Page(s) tgab029

Abstract: The nucleus reuniens and rhomboid nuclei of the thalamus (ReRh) are reciprocally connected to a range of higher order cortices including hippocampus (HPC) and medial prefrontal cortex (mPFC). The physiological function of ReRh is well predicted by ... ...

Abstract	The nucleus reuniens and rhomboid nuclei of the thalamus (ReRh) are reciprocally connected to a range of higher order cortices including hippocampus (HPC) and medial prefrontal cortex (mPFC). The physiological function of ReRh is well predicted by requirement for interactions between mPFC and HPC, including associative recognition memory, spatial navigation, and working memory. Although anatomical and electrophysiological evidence suggests ReRh makes excitatory synapses in mPFC there is little data on the physiological properties of these projections, or whether ReRh and HPC target overlapping cell populations and, if so, how they interact. We demonstrate in ex vivo mPFC slices that ReRh and HPC afferent inputs converge onto more than two-thirds of layer 5 pyramidal neurons, show that ReRh, but not HPC, undergoes marked short-term plasticity during theta frequency transmission, and that HPC, but not ReRh, afferents are subject to neuromodulation by acetylcholine acting via muscarinic receptor M2. Finally, we demonstrate that pairing HPC followed by ReRh (but not pairing ReRh followed by HPC) at theta frequency induces associative, NMDA receptor dependent synaptic plasticity in both inputs to mPFC. These data provide vital physiological phenotypes of the synapses of this circuit and provide a novel mechanism for HPC-ReRh-mPFC encoding.
Language	English
Publishing date	2021-04-14
Publishing country	United States
Document type	Journal Article
ISSN	2632-7376
ISSN (online)	2632-7376
DOI	10.1093/texcom/tgab029
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Article ; Online: Impaired hippocampal NMDAR-LTP in a transgenic model of NSUN2-deficiency.

George, Harry / Bashir, Zafar I / Hussain, Shobbir

Neurobiology of disease

2021 Volume 163, Page(s) 105597

Abstract: Biallelic loss-of-function NSUN2 mutations have recently been associated with cases of Autism Spectrum Condition (ASC), and NSun2-deficiency was also previously shown to cause a severe autosomal recessive intellectually disability disorder syndrome in ... ...

Abstract	Biallelic loss-of-function NSUN2 mutations have recently been associated with cases of Autism Spectrum Condition (ASC), and NSun2-deficiency was also previously shown to cause a severe autosomal recessive intellectually disability disorder syndrome in which patients can sometimes display autistic behaviour. It has been demonstrated that NSUN2 can control protein synthesis rates via direct regulation of RNA methylation, and it is therefore of interest that other studies have suggested protein synthesis-dependent synaptic plasticity dysregulation as a mechanism for learning difficulties in various other autism-expressing conditions and disorders. Here we investigated NMDAR-LTP in a murine transgenic model harbouring loss-of-function mutation in the NSun2 gene and find an impairment of a protein synthesis-dependent form of this synaptic plasticity pathway. Our findings support the idea that NMDAR-LTP mis-regulation may represent a previously underappreciated mechanism associated with autism phenotypes.
MeSH term(s)	Animals ; Autism Spectrum Disorder/genetics ; Autism Spectrum Disorder/metabolism ; Hippocampus/metabolism ; Intellectual Disability/genetics ; Intellectual Disability/metabolism ; Long-Term Potentiation/genetics ; Methyltransferases/genetics ; Methyltransferases/metabolism ; Mice ; Mice, Transgenic ; Mutation ; Receptors, N-Methyl-D-Aspartate/physiology
Chemical Substances	Receptors, N-Methyl-D-Aspartate ; Methyltransferases (EC 2.1.1.-) ; Misu protein, mouse (EC 2.1.1.-)
Language	English
Publishing date	2021-12-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2021.105597
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Article ; Online: Cerebellar Prediction and Feeding Behaviour.

Iosif, Cristiana I / Bashir, Zafar I / Apps, Richard / Pickford, Jasmine

Cerebellum (London, England)

2022 Volume 22, Issue 5, Page(s) 1002–1019

Abstract: Given the importance of the cerebellum in controlling movements, it might be expected that its main role in eating would be the control of motor elements such as chewing and swallowing. Whilst such functions are clearly important, there is more to eating ...

Abstract	Given the importance of the cerebellum in controlling movements, it might be expected that its main role in eating would be the control of motor elements such as chewing and swallowing. Whilst such functions are clearly important, there is more to eating than these actions, and more to the cerebellum than motor control. This review will present evidence that the cerebellum contributes to homeostatic, motor, rewarding and affective aspects of food consumption.Prediction and feedback underlie many elements of eating, as food consumption is influenced by expectation. For example, circadian clocks cause hunger in anticipation of a meal, and food consumption causes feedback signals which induce satiety. Similarly, the sight and smell of food generate an expectation of what that food will taste like, and its actual taste will generate an internal reward value which will be compared to that expectation. Cerebellar learning is widely thought to involve feed-forward predictions to compare expected outcomes to sensory feedback. We therefore propose that the overarching role of the cerebellum in eating is to respond to prediction errors arising across the homeostatic, motor, cognitive, and affective domains.
MeSH term(s)	Feeding Behavior ; Hunger ; Satiation ; Cerebellum ; Learning ; Eating
Language	English
Publishing date	2022-09-19
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2112586-7
ISSN	1473-4230 ; 1473-4222
ISSN (online)	1473-4230
ISSN	1473-4222
DOI	10.1007/s12311-022-01476-3
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Zs.A 5795: Show issues

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Article: Presynaptic NR2A-Containing NMDARs Are Required for LTD between the Amygdala and the Perirhinal Cortex: A Potential Mechanism for the Emotional Modulation of Memory?(1,2,3).

Laing, Michael D / Bashir, Zafar I

eNeuro

2015 Volume 2, Issue 1

Abstract: Visual recognition memory relies on long-term depression-like mechanisms within the perirhinal cortex and the activation of the lateral amygdala can enhance visual recognition memory. How the lateral amygdala regulates recognition memory is not known, ... ...

Abstract	Visual recognition memory relies on long-term depression-like mechanisms within the perirhinal cortex and the activation of the lateral amygdala can enhance visual recognition memory. How the lateral amygdala regulates recognition memory is not known, but synaptic plasticity at amygdala-perirhinal synapses may provide a mechanism for the emotional enhancement of recognition memory. In this study, we investigate the mechanisms of long-term depression (LTD) at the amygdala-perirhinal synapse in male Lister Hooded rats. We demonstrate that LTD at this input relies on NR2A-containing NMDARs, located presynaptically. Therefore, the underlying mechanisms of LTD, at the amygdala-perirhinal input, which may regulate the emotional context for recognition memory, are different to previously described postsynaptic NR2B-NMDAR mechanisms of intraperirhinal LTD that subserve recognition memory.
Language	English
Publishing date	2015-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2800598-3
ISSN	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0046-14.2015
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Article: The epitranscriptome in modulating spatiotemporal RNA translation in neuronal post-synaptic function.

Hussain, Shobbir / Bashir, Zafar I

Frontiers in cellular neuroscience

2015 Volume 9, Page(s) 420

Abstract: The application of next-generation-sequencing based methods has recently allowed the sequence-specific occurrence of RNA modifications to be investigated in transcriptome-wide settings. This has led to the emergence of a new field of molecular genetics ... ...

Abstract	The application of next-generation-sequencing based methods has recently allowed the sequence-specific occurrence of RNA modifications to be investigated in transcriptome-wide settings. This has led to the emergence of a new field of molecular genetics research termed "epitranscriptomics." Investigations have shown that these modifications can exert control over protein synthesis via various mechanisms, and particularly when occurring on messenger RNAs, can be dynamically regulated. Here, we propose that RNA modifications may be a critical regulator over the spatiotemporal control of protein-synthesis in neurons, which is supported by our finding that the RNA methylase NSun2 colocalizes with the translational-repressor FMRP at neuronal dendrites. We also observe that NSun2 commonly methylates mRNAs which encode components of the postsynaptic proteome, and further find that NSun2 and FMRP likely share a common subset of mRNA targets which include those that are known to be translated at dendrites in an activity-dependent manner. We consider potential roles for RNA modifications in space- time- and activity-dependent regulation of protein synthesis in neuronal physiology, with a particular focus on synaptic plasticity modulation.
Language	English
Publishing date	2015-10-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2015.00420
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Article ; Online: Mechanisms of mGluR-dependent plasticity in hippocampal area CA2.

Samadi, Mahsa / Hales, Claire A / Lustberg, Daniel J / Farris, Shannon / Ross, Madeleine R / Zhao, Meilan / Hepler, John R / Harbin, Nicholas H / Robinson, Emma S J / Banks, Paul J / Bashir, Zafar I / Dudek, Serena M

Hippocampus

2023 Volume 33, Issue 6, Page(s) 730–744

Abstract: Pyramidal cells in hippocampal area CA2 have synaptic properties that are distinct from the other CA subregions. Notably, this includes a lack of typical long-term potentiation of stratum radiatum synapses. CA2 neurons express high levels of several ... ...

Abstract	Pyramidal cells in hippocampal area CA2 have synaptic properties that are distinct from the other CA subregions. Notably, this includes a lack of typical long-term potentiation of stratum radiatum synapses. CA2 neurons express high levels of several known and potential regulators of metabotropic glutamate receptor (mGluR)-dependent signaling including Striatal-Enriched Tyrosine Phosphatase (STEP) and several Regulator of G-protein Signaling (RGS) proteins, yet the functions of these proteins in regulating mGluR-dependent synaptic plasticity in CA2 are completely unknown. Thus, the aim of this study was to examine mGluR-dependent synaptic depression and to determine whether STEP and the RGS proteins RGS4 and RGS14 are involved. Using whole cell voltage-clamp recordings from mouse pyramidal cells, we found that mGluR agonist-induced long-term depression (mGluR-LTD) is more pronounced in CA2 compared with that observed in CA1. This mGluR-LTD in CA2 was found to be protein synthesis and STEP dependent, suggesting that CA2 mGluR-LTD shares mechanistic processes with those seen in CA1, but in addition, RGS14, but not RGS4, was essential for mGluR-LTD in CA2. In addition, we found that exogenous application of STEP could rescue mGluR-LTD in RGS14 KO slices. Supporting a role for CA2 synaptic plasticity in social cognition, we found that RGS14 KO mice had impaired social recognition memory as assessed in a social discrimination task. These results highlight possible roles for mGluRs, RGS14, and STEP in CA2-dependent behaviors, perhaps by biasing the dominant form of synaptic plasticity away from LTP and toward LTD in CA2.
MeSH term(s)	Animals ; Mice ; Hippocampus/physiology ; Long-Term Potentiation/physiology ; Long-Term Synaptic Depression/physiology ; Neuronal Plasticity ; Pyramidal Cells/physiology ; Receptors, Metabotropic Glutamate/metabolism ; RGS Proteins/genetics ; RGS Proteins/metabolism
Chemical Substances	Receptors, Metabotropic Glutamate ; RGS Proteins ; Rgs14 protein, mouse ; Ptpn5 protein, mouse (EC 3.1.3.48)
Language	English
Publishing date	2023-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1074352-2
ISSN	1098-1063 ; 1050-9631
ISSN (online)	1098-1063
ISSN	1050-9631
DOI	10.1002/hipo.23529
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Zs.A 3227: Show issues

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Article ; Online: Nicotinic Acetylcholine Receptors Control Encoding and Retrieval of Associative Recognition Memory through Plasticity in the Medial Prefrontal Cortex.

Sabec, Marie H / Wonnacott, Susan / Warburton, E Clea / Bashir, Zafar I

Cell reports

2018 Volume 22, Issue 13, Page(s) 3409–3415

Abstract: Nicotinic acetylcholine receptors (nAChRs) expressed in the medial prefrontal cortex have critical roles in cognitive function. However, whether nAChRs are required for associative recognition memory and the mechanisms by which nAChRs may contribute to ... ...

Abstract	Nicotinic acetylcholine receptors (nAChRs) expressed in the medial prefrontal cortex have critical roles in cognitive function. However, whether nAChRs are required for associative recognition memory and the mechanisms by which nAChRs may contribute to mnemonic processing are not known. We demonstrate that nAChRs in the prefrontal cortex exhibit subtype-specific roles in associative memory encoding and retrieval. We present evidence that these separate roles of nAChRs may rely on bidirectional modulation of plasticity at synaptic inputs to the prefrontal cortex that are essential for associative recognition memory.
MeSH term(s)	Animals ; Association Learning/physiology ; Male ; Memory/physiology ; Neuronal Plasticity/physiology ; Prefrontal Cortex/metabolism ; Rats ; Receptors, AMPA/metabolism ; Receptors, Nicotinic/metabolism
Chemical Substances	Receptors, AMPA ; Receptors, Nicotinic ; glutamate receptor ionotropic, AMPA 2 (P6W5IXV8V9)
Language	English
Publishing date	2018-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2018.03.016
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Article ; Online: Regionally selective requirement for D1/D5 dopaminergic neurotransmission in the medial prefrontal cortex in object-in-place associative recognition memory.

Savalli, Giorgia / Bashir, Zafar I / Warburton, E Clea

Learning & memory (Cold Spring Harbor, N.Y.)

2015 Volume 22, Issue 2, Page(s) 69–73

Abstract: Object-in-place (OiP) memory is critical for remembering the location in which an object was last encountered and depends conjointly on the medial prefrontal cortex, perirhinal cortex, and hippocampus. Here we examined the role of dopamine D1/D5 receptor ...

Abstract	Object-in-place (OiP) memory is critical for remembering the location in which an object was last encountered and depends conjointly on the medial prefrontal cortex, perirhinal cortex, and hippocampus. Here we examined the role of dopamine D1/D5 receptor neurotransmission within these brain regions for OiP memory. Bilateral infusion of D1/D5 receptor antagonists SCH23390 or SKF83566 into the medial prefrontal cortex, prior to memory acquisition, impaired OiP performance following a 5 min or 1 h delay. Retrieval was unaffected. Intraperirhinal or intrahippocampal infusions of SCH23390 had no effect. These results reveal a selective role for D1/D5 receptors in the mPFC during OiP memory encoding.
MeSH term(s)	2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/analogs & derivatives ; 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology ; Animals ; Association Learning/drug effects ; Association Learning/physiology ; Benzazepines/pharmacology ; Dopamine Antagonists/pharmacology ; Male ; Prefrontal Cortex/drug effects ; Prefrontal Cortex/physiology ; Rats ; Receptors, Dopamine D1/antagonists & inhibitors ; Receptors, Dopamine D1/physiology ; Receptors, Dopamine D5/antagonists & inhibitors ; Receptors, Dopamine D5/physiology ; Recognition, Psychology/drug effects ; Recognition, Psychology/physiology ; Spatial Memory/drug effects ; Spatial Memory/physiology ; Synaptic Transmission/drug effects
Chemical Substances	Benzazepines ; Dopamine Antagonists ; Receptors, Dopamine D1 ; SCH 23390 ; Receptors, Dopamine D5 (137750-35-7) ; 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (67287-49-4) ; 1H-3-benzazepin-7-ol, 8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl- (D203LR7XUS)
Language	English
Publishing date	2015-01-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1204777-6
ISSN	1549-5485 ; 1072-0502
ISSN (online)	1549-5485
ISSN	1072-0502
DOI	10.1101/lm.036921.114
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