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Article: The Contribution of Hippocampal All-Trans Retinoic Acid (ATRA) Deficiency to Alzheimer's Disease: A Narrative Overview of ATRA-Dependent Gene Expression in Post-Mortem Hippocampal Tissue.

Almaguer, Joey / Hindle, Ashly / Lawrence, J Josh

2023 Volume 12, Issue 11

Abstract: There is accumulating evidence that vitamin A (VA) deficiency contributes to the pathogenesis and progression of Alzheimer's disease (AD). All- ...

Abstract	There is accumulating evidence that vitamin A (VA) deficiency contributes to the pathogenesis and progression of Alzheimer's disease (AD). All-
Language	English
Publishing date	2023-10-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12111921
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Article ; Online: Cancer drugs with high repositioning potential for Alzheimer's disease.

Majeed, Jad / Sabbagh, Marwan N / Kang, Min H / Lawrence, J Josh / Pruitt, Kevin / Bacus, Sarah / Reyna, Ellie / Brown, Maddy / Decourt, Boris

Expert opinion on emerging drugs

2023 Volume 28, Issue 4, Page(s) 311–332

Abstract: Introduction: Despite the recent full FDA approval of lecanemab, there is currently no disease modifying therapy (DMT) that can efficiently slow down the progression of Alzheimer's disease (AD) in the general population. This statement emphasizes the ... ...

Abstract	Introduction: Despite the recent full FDA approval of lecanemab, there is currently no disease modifying therapy (DMT) that can efficiently slow down the progression of Alzheimer's disease (AD) in the general population. This statement emphasizes the need to identify novel DMTs in the shortest time possible to prevent a global epidemic of AD cases as the world population experiences an increase in lifespan. Areas covered: Here, we review several classes of anti-cancer drugs that have been or are being investigated in Phase II/III clinical trials for AD, including immunomodulatory drugs, RXR agonists, sex hormone therapies, tyrosine kinase inhibitors, and monoclonal antibodies. Expert opinion: Given the overall course of brain pathologies during the progression of AD, we express a great enthusiasm for the repositioning of anti-cancer drugs as possible AD DMTs. We anticipate an increasing number of combinatorial therapy strategies to tackle AD symptoms and their underlying pathologies. However, we strongly encourage improvements in clinical trial study designs to better assess target engagement and possible efficacy over sufficient periods of drug exposure.
MeSH term(s)	Humans ; Alzheimer Disease/drug therapy ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/therapeutic use ; Drug Repositioning
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents
Language	English
Publishing date	2023-12-26
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2061369-6
ISSN	1744-7623 ; 1472-8214
ISSN (online)	1744-7623
ISSN	1472-8214
DOI	10.1080/14728214.2023.2296079
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Article ; Online: Associations Between Vitamin D Deficiency/Insufficiency and Depression Expose Health Disparities in Older Rural West Texans: A Project FRONTIER Study.

Pourghaed, Mohammed / Sarangi, Ashish / Ramirez-Velandia, Felipe / Kopel, Jonathan / Culberson, John / Ashworth, Gabriela / Khan, Hafiz / Boles, Annette / Neugebauer, Volker / Lawrence, J Josh

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry

2024

Abstract: Objective: To determine associations between Vitamin D (VD) levels and clinical depression through the Geriatric Depression Scale (GDS) and its questions and subdomains, stratified by demographics and Hispanic/Latino ethnicity (HLE).: Design, setting, ...

Abstract	Objective: To determine associations between Vitamin D (VD) levels and clinical depression through the Geriatric Depression Scale (GDS) and its questions and subdomains, stratified by demographics and Hispanic/Latino ethnicity (HLE). Design, setting, and participants: A cohort of 299 Project FRONTIER participants aged 62.6 ± 11.7 years old, 70.9% female, and 40.5% HLE were used. Standard correlation and regression analyses were employed. Measurements: The main outcome measures were VD (serum 25(OH)-VD) level, GDS-30 (30-item questionnaire), GDS-30 subfactors and questions, and HLE status. VD categories were defined as VD deficiency (VDD; ≤20 ng/mL), VD insufficiency (VDI; 21-29 ng/mL), VD sufficiency (30-38 ng/mL) and high VD sufficiency (>38 ng/mL). Results: The majority (61.5%) of samples fell into VDD/VDI categories. A significant negative association was found between VD level and GDS-30 total score. VD level was negatively correlated with Dysphoria and Meaninglessness GDS-30 subfactors. Although GDS subfactors were similar between HLE and non-HLE groups, VD levels were significantly lower in HLE samples. Finally, HLE/non-HLE groups were differentially stratified across VD categories. Only 4% of HLEs fell into the high VD sufficient category, suggesting low VD supplementation. Conclusion: A significant negative association between VD level and depressive symptoms was revealed in our aging Project FRONTIER participants. HLE individuals were overrepresented in VDD/VDI samples, and VDD/VDI was associated primarily with the Dysphoria GDS subdomain. Regression analysis predicted high VD sufficiency (95.5 ng/mL) to be associated with no depressive symptoms (GDS=0). Our results underscore troubling disparities in VD-related depressive symptoms between HLE and non-HLE populations.
Language	English
Publishing date	2024-01-26
Publishing country	England
Document type	Journal Article
ZDB-ID	1278145-9
ISSN	1545-7214 ; 1064-7481
ISSN (online)	1545-7214
ISSN	1064-7481
DOI	10.1016/j.jagp.2024.01.029
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Article ; Online: Septohippocampal transmission from parvalbumin-positive neurons features rapid recovery from synaptic depression.

Yi, Feng / Garrett, Tavita / Deisseroth, Karl / Haario, Heikki / Stone, Emily / Lawrence, J Josh

Scientific reports

2021 Volume 11, Issue 1, Page(s) 2117

Abstract: Parvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca ([Formula: see text]) are essential for hippocampal rhythms and learning operations yet are poorly understood at cellular and synaptic levels. We combined ... ...

Abstract	Parvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca ([Formula: see text]) are essential for hippocampal rhythms and learning operations yet are poorly understood at cellular and synaptic levels. We combined electrophysiological, optogenetic, and modeling approaches to investigate [Formula: see text] neuronal properties. [Formula: see text] neurons had intrinsic membrane properties distinct from acetylcholine- and somatostatin-containing MS-DBB subtypes. Viral expression of the fast-kinetic channelrhodopsin ChETA-YFP elicited action potentials to brief (1-2 ms) 470 nm light pulses. To investigate [Formula: see text] transmission, light pulses at 5-50 Hz frequencies generated trains of inhibitory postsynaptic currents (IPSCs) in CA1 stratum oriens interneurons. Using a similar approach, optogenetic activation of local hippocampal PV ([Formula: see text]) neurons generated trains of [Formula: see text]-mediated IPSCs in CA1 pyramidal neurons. Both synapse types exhibited short-term depression (STD) of IPSCs. However, relative to [Formula: see text] synapses, [Formula: see text] synapses possessed lower initial release probability, transiently resisted STD at gamma (20-50 Hz) frequencies, and recovered more rapidly from synaptic depression. Experimentally-constrained mathematical synapse models explored mechanistic differences. Relative to the [Formula: see text] model, the [Formula: see text] model exhibited higher sensitivity to calcium accumulation, permitting a faster rate of calcium-dependent recovery from STD. In conclusion, resistance of [Formula: see text] synapses to STD during short gamma bursts enables robust long-range GABAergic transmission from MS-DBB to hippocampus.
MeSH term(s)	Algorithms ; Animals ; Calcium/metabolism ; Hippocampus/cytology ; Hippocampus/physiology ; Membrane Potentials/physiology ; Mice, Transgenic ; Models, Neurological ; Neurons/cytology ; Neurons/metabolism ; Neurons/physiology ; Optogenetics/methods ; Parvalbumins/metabolism ; Patch-Clamp Techniques ; Septum of Brain/cytology ; Septum of Brain/physiology ; Synapses/physiology ; Synaptic Transmission/physiology
Chemical Substances	Parvalbumins ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-01-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-80245-w
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Article: Effect of Neuromodulation of Short-term Plasticity on Information Processing in Hippocampal Interneuron Synapses.

Bayat Mokhtari, Elham / Lawrence, J Josh / Stone, Emily F

Journal of mathematical neuroscience

2018 Volume 8, Issue 1, Page(s) 7

Abstract: Neurons in a micro-circuit connected by chemical synapses can have their connectivity affected by the prior activity of the cells. The number of synapses available for releasing neurotransmitter can be decreased by repetitive activation through depletion ...

Abstract	Neurons in a micro-circuit connected by chemical synapses can have their connectivity affected by the prior activity of the cells. The number of synapses available for releasing neurotransmitter can be decreased by repetitive activation through depletion of readily releasable neurotransmitter (NT), or increased through facilitation, where the probability of release of NT is increased by prior activation. These competing effects can create a complicated and subtle range of time-dependent connectivity. Here we investigate the probabilistic properties of facilitation and depression (FD) for a presynaptic neuron that is receiving a Poisson spike train of input. We use a model of FD that is parameterized with experimental data from a hippocampal basket cell and pyramidal cell connection, for fixed frequency input spikes at frequencies in the range of theta (3-8 Hz) and gamma (20-100 Hz) oscillations. Hence our results will apply to micro-circuits in the hippocampus that are responsible for the interaction of theta and gamma rhythms associated with learning and memory. A control situation is compared with one in which a pharmaceutical neuromodulator (muscarine) is employed. We apply standard information-theoretic measures such as entropy and mutual information, and find a closed form approximate expression for the probability distribution of release probability. We also use techniques that measure the dependence of the response on the exact history of stimulation the synapse has received, which uncovers some unexpected differences between control and muscarine-added cases.
Language	English
Publishing date	2018-05-29
Publishing country	Germany
Document type	Journal Article
ISSN	2190-8567
ISSN	2190-8567
DOI	10.1186/s13408-018-0062-z
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Article: Data Driven Models of Short-Term Synaptic Plasticity.

Bayat Mokhtari, Elham / Lawrence, J Josh / Stone, Emily F

Frontiers in computational neuroscience

2018 Volume 12, Page(s) 32

Abstract: Simple models of short term synaptic plasticity that incorporate facilitation and/or depression have been created in abundance for different synapse types and circumstances. The analysis of these models has included computing mutual information between a ...

Abstract	Simple models of short term synaptic plasticity that incorporate facilitation and/or depression have been created in abundance for different synapse types and circumstances. The analysis of these models has included computing mutual information between a stochastic input spike train and some sort of representation of the postsynaptic response. While this approach has proven useful in many contexts, for the purpose of determining the type of process underlying a stochastic output train, it ignores the ordering of the responses, leaving an important characterizing feature on the table. In this paper we use a broader class of information measures on output only, and specifically construct hidden Markov models (HMMs) (known as epsilon machines or causal state models) to differentiate between synapse type, and classify the complexity of the process. We find that the machines allow us to differentiate between processes in a way not possible by considering distributions alone. We are also able to understand these differences in terms of the dynamics of the model used to create the output response, bringing the analysis full circle. Hence this technique provides a complimentary description of the synaptic filtering process, and potentially expands the interpretation of future experimental results.
Language	English
Publishing date	2018-05-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452964-3
ISSN	1662-5188
ISSN	1662-5188
DOI	10.3389/fncom.2018.00032
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Article: Cholinergic control of GABA release: emerging parallels between neocortex and hippocampus.

Lawrence, J Josh

Trends in neurosciences

2008 Volume 31, Issue 7, Page(s) 317–327

Abstract: Release of acetylcholine (ACh) into the neocortex and hippocampus profoundly alters cellular excitability, network synchronization and behavioral state. Despite its diverse cellular and synaptic targets, the actions of ACh can be highly specific, ... ...

Abstract	Release of acetylcholine (ACh) into the neocortex and hippocampus profoundly alters cellular excitability, network synchronization and behavioral state. Despite its diverse cellular and synaptic targets, the actions of ACh can be highly specific, altering the excitability of distinct inhibitory and excitatory cell types. This review presents evidence for the selectivity of cholinergic neuromodulation in GABAergic interneurons and identifies emerging parallels between the neocortex and hippocampus. In light of growing evidence that neuromodulatory specializations relate to neurochemical identity, I propose that differential engagement of neurochemically distinct interneuron subtypes is a unifying principle by which ACh orchestrates the flow of sensory information in the neocortex and hippocampus.
MeSH term(s)	Acetylcholine/metabolism ; Animals ; Hippocampus/cytology ; Hippocampus/metabolism ; Humans ; Interneurons/cytology ; Interneurons/metabolism ; Neocortex/cytology ; Neocortex/metabolism ; Synaptic Transmission/physiology ; gamma-Aminobutyric Acid/secretion
Chemical Substances	gamma-Aminobutyric Acid (56-12-2) ; Acetylcholine (N9YNS0M02X)
Language	English
Publishing date	2008-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	282488-7
ISSN	1878-108X ; 0166-2236 ; 0378-5912
ISSN (online)	1878-108X
ISSN	0166-2236 ; 0378-5912
DOI	10.1016/j.tins.2008.03.008
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Zs.A 1442: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Homosynaptic and heterosynaptic modes of endocannabinoid action at hippocampal CCK+ basket cell synapses.

Lawrence, J Josh

The Journal of physiology

2007 Volume 578, Issue Pt 1, Page(s) 3–4

MeSH term(s)	Animals ; Cannabinoid Receptor Modulators/physiology ; Cholecystokinin/physiology ; Endocannabinoids ; Hippocampus/cytology ; Hippocampus/physiology ; Interneurons/physiology ; Rats ; Receptor, Cannabinoid, CB1/physiology ; Synapses/physiology
Chemical Substances	Cannabinoid Receptor Modulators ; Endocannabinoids ; Receptor, Cannabinoid, CB1 ; Cholecystokinin (9011-97-6)
Language	English
Publishing date	2007-01-01
Publishing country	England
Document type	Comment ; Journal Article
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/jphysiol.2006.123802
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Article ; Online: Presynaptic cholinergic neuromodulation alters the temporal dynamics of short-term depression at parvalbumin-positive basket cell synapses from juvenile CA1 mouse hippocampus.

Lawrence, J Josh / Haario, Heikki / Stone, Emily F

Journal of neurophysiology

2015 Volume 113, Issue 7, Page(s) 2408–2419

Abstract: Parvalbumin-positive basket cells (PV BCs) of the CA1 hippocampus are active participants in theta (5-12 Hz) and gamma (20-80 Hz) oscillations in vivo. When PV BCs are driven at these frequencies in vitro, inhibitory postsynaptic currents (IPSCs) in ... ...

Abstract	Parvalbumin-positive basket cells (PV BCs) of the CA1 hippocampus are active participants in theta (5-12 Hz) and gamma (20-80 Hz) oscillations in vivo. When PV BCs are driven at these frequencies in vitro, inhibitory postsynaptic currents (IPSCs) in synaptically connected CA1 pyramidal cells exhibit paired-pulse depression (PPD) and multiple-pulse depression (MPD). Moreover, PV BCs express presynaptic muscarinic acetylcholine receptors (mAChRs) that may be activated by synaptically released acetylcholine during learning behaviors in vivo. Using acute hippocampal slices from the CA1 hippocampus of juvenile PV-GFP mice, we performed whole cell recordings from synaptically connected PV BC-CA1 pyramidal cell pairs to investigate how bath application of 10 μM muscarine impacts PPD and MPD at CA1 PV BC-pyramidal cell synapses. In accordance with previous studies, PPD and MPD magnitude increased with stimulation frequency. mAChR activation reduced IPSC amplitude and transiently reduced PPD, but MPD was largely maintained. Consistent with a reduction in release probability (pr), MPD and mAChR activation increased both the coefficient of variation of IPSC amplitudes and the fraction of failures. Using variance-mean analysis, we converted MPD trains to pr functions and developed a kinetic model that optimally fit six distinct pr conditions. The model revealed that vesicular depletion caused MPD and that recovery from depression was dependent on calcium. mAChR activation reduced the presynaptic calcium transient fourfold and initial pr twofold, thereby reducing PPD. However, mAChR activation slowed calcium-dependent recovery from depression during sustained repetitive activity, thereby preserving MPD. Thus the activation of presynaptic mAChRs optimally protects PV BCs from vesicular depletion during short bursts of high-frequency activity.
MeSH term(s)	Animals ; Cells, Cultured ; Cholinergic Neurons/cytology ; Cholinergic Neurons/physiology ; GABAergic Neurons/cytology ; GABAergic Neurons/physiology ; Hippocampus/cytology ; Hippocampus/physiology ; Interneurons/cytology ; Interneurons/physiology ; Long-Term Synaptic Depression/physiology ; Mice ; Parvalbumins/metabolism ; Presynaptic Terminals/physiology ; Receptors, Muscarinic/metabolism ; Spatio-Temporal Analysis
Chemical Substances	Parvalbumins ; Receptors, Muscarinic
Language	English
Publishing date	2015-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00167.2014
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Article ; Online: Enteric plexuses of two choline-acetyltransferase transgenic mouse lines: chemical neuroanatomy of the fluorescent protein-expressing nerve cells.

Wilhelm, Márta / Lawrence, J Josh / Gábriel, Robert

Brain research bulletin

2015 Volume 111, Page(s) 76–83

Abstract: We studied cholinergic circuit elements in the enteric nervous system (ENS) of two distinct transgenic mouse lines in which fluorescent protein expression was driven by the choline-acetyltransferase (ChAT) promoter. In the first mouse line, green ... ...

Abstract	We studied cholinergic circuit elements in the enteric nervous system (ENS) of two distinct transgenic mouse lines in which fluorescent protein expression was driven by the choline-acetyltransferase (ChAT) promoter. In the first mouse line, green fluorescent protein was fused to the tau gene. This construct allowed the visualization of the fiber tracts and ganglia, however the nerve cells were poorly resolved. In the second mouse line (ChATcre-YFP), CRE/loxP recombination yielded cytosolic expression of yellow fluorescent protein (YFP). In these preparations the morphology of enteric neurons could be well studied. We also determined the neurochemical identity of ENS neurons in muscular and submucous layers using antibodies against YFP, calretinin (CALR), calbindin (CALB), and vasoactive intestinal peptide (VIP). Confocal microscopic imaging was used to visualize fluorescently-conjugated secondary antibodies. In ChATcre-YFP preparations, YFP was readily apparent in somatodendritic regions of ENS neurons. In the myenteric plexus, YFP/CALR/VIP staining revealed that 34% of cholinergic cells co-labeled with CALR. Few single-stained CR-positive cells were observed. Neither YFP nor CALR co-localized with VIP. In GFP/CALB/CALR staining, all co-localization combinations were represented. In the submucosal plexus, YFP/CALR/VIP staining revealed discrete neuronal populations. However, in separate preparations, double labeling was observed for YFP/CALR and CALR/VIP. In YFP/CALR/CALB staining, all combinations of double staining and triple labeling were verified. In conclusion, the neurochemical coding of ENS neurons in these mouse lines is consistent with many observations in non-transgenic animals. Thus, they provide useful tools for physiological and pharmacological studies on distinct neurochemical subtypes of ENS neurons.
MeSH term(s)	Animals ; Bacterial Proteins/analysis ; Calbindin 2/analysis ; Calbindins/analysis ; Choline O-Acetyltransferase/analysis ; Cholinergic Neurons/metabolism ; Enteric Nervous System/cytology ; Enteric Nervous System/metabolism ; Fluorescent Dyes ; Green Fluorescent Proteins/analysis ; Immunohistochemistry/methods ; Luminescent Proteins/analysis ; Mice ; Mice, Transgenic ; Neuroanatomical Tract-Tracing Techniques/methods ; Neurons/cytology ; Neurons/metabolism ; Promoter Regions, Genetic ; Vasoactive Intestinal Peptide/analysis ; tau Proteins/genetics
Chemical Substances	Bacterial Proteins ; Calbindin 2 ; Calbindins ; Fluorescent Dyes ; Luminescent Proteins ; Mapt protein, mouse ; tau Proteins ; yellow fluorescent protein, Bacteria ; Green Fluorescent Proteins (147336-22-9) ; Vasoactive Intestinal Peptide (37221-79-7) ; Choline O-Acetyltransferase (EC 2.3.1.6)
Language	English
Publishing date	2015-01-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	197620-5
ISSN	1873-2747 ; 0361-9230
ISSN (online)	1873-2747
ISSN	0361-9230
DOI	10.1016/j.brainresbull.2015.01.001
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