Age-related changes in medial septal cholinergic and GABAergic projection neurons and hippocampal neurotransmitter receptors: relationship with memory impairment

Burjanadze, M.; Dashniani, M.; Solomonia, Revaz; Beselia, G.; Tsverava, Lia; Lagani, Vincenzo; Chkhikvishvili, N.; Naneishvili, T.; Kruashvili, L.; Chighladze, M.

doi:10.1007/s00221-022-06354-2

Cited by 8 publications

(4 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous studies, inactivation of medial septum (MS) reduced theta rhythm and disrupted grid firing in MEC 40,41 . Although we could not exclude the possibility of neuronal loss and other chronic changes in aged MS that eventually impacted grid firing in aging MEC 55,56 , our observation on unstable firing of other spatial coding cells such as head direction cells and speed cells that often are not impacted by theta rhythms, support the conclusion that local changes happening in MEC during aging, including grid cells. The reduction in slow gamma power in aging MEC provides evidence of unstable coding of place cells in the hippocampus in aged rodents 57 , since coordination of gamma between MEC and hippocampus is crucial for memory coding and retrieval 58 .…”

Section: Discussionmentioning

confidence: 57%

Cellular and Molecular Changes During Aging in MEC: Unveiling the Role of Bglap3 Neurons in Cognitive Aging

Cao,

Uzeen,

Cheng

et al. 2024

Preprint

View full text Add to dashboard Cite

SummaryAging-correlated cognitive declines, including deficiencies in spatial orientation and memory, may reflect dysfunction in the hippocampus and medial entorhinal cortex (MEC). However, aging-related changes in MEC at the cellular and molecular levels remain unclear. In this study, we found fewer grid cells with reduced spatial stability in old mice. We compared gene expression profiles between young and old mice using 10x Genomics Visium technology. Among 1664 differentially expressed genes, we discovered Bglap3, a marker gene for subpopulation in MEC Layer III with decreased cell number with age. Silencing of Bglap3+ neurons in young mice impaired the spatial tuning of neurons in MEC and the spatial learning of a new platform location in water maze. These findings help us to understand the cellular and molecular changes in the MEC in healthy aging animals and the changes of Bglap3+ cells in old mice indicating a possible cause of aging-related MEC deficiency.

show abstract

Section: Discussionmentioning

confidence: 57%

Cellular and Molecular Changes During Aging in MEC: Unveiling the Role of Bglap3 Neurons in Cognitive Aging

Cao,

Uzeen,

Cheng

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Regarding the underlying neurobiology of the aged EdM phenotype, we also present results in parallel from a preliminary investigation inspired by recent studies into the role of age-related alteration of the endocannabinoid system in mnemonic decline (Bilkei-Gorzo, 2012;Bilkei-Gorzo et al, 2017). Notably, using the Dlx-CB1-KO transgenic mouse line (Monory et al, 2006), we provide the first evidence of a critical role for cannabinoid type-I receptors expressed on GABAergic neurons of the forebrain (whose signaling is known to alter with age, diminishing or augmenting depending on the area considered: Burjanadze et al, 2022;Ethiraj et al, 2021;Pandya et al, 2019) in successful active forgetting-dependent EdM performance. We observed that Dlx-CB1-KO mice present an extreme version of the aged EdM phenotype while wildtype animals replicate the behavioral profile of young mice.…”

Section: Resultsmentioning

confidence: 72%

To deliberate, remember; to anticipate, forget: Cognitive deliberation profiles underpinning active forgetting-dependent everyday-like memory performance in young and aged mice

Stevens

Abed

Sellami

et al. 2023

Preprint

View full text Add to dashboard Cite

Recalling a specific past episode that will enable us to decide which action is suited to a given present situation is a core element of everyday life. A wealth of research has demonstrated that such selective remembering is dependent upon a capacity to inhibit or provisionally 'forget' related yet inappropriate memory episodes which could orient behavior in unwilled directions. Everyday-like memory (EdM) refers to this type of common organizational mnemonic capacity, known to deteriorate significantly with age, putatively as a result of decline in the cognitive capacity for selective inhibition or 'active forgetting'. Moreover, this memory retrieval-concomitant active forgetting comes at the cost of genuine amnesic weakening of the inhibited episodes, a phenomenon referred to as retrieval-induced forgetting (RIF). In the present study, we introduce a novel characterization of our previously validated mouse model of EdM in terms of the existing active forgetting and RIF literature. We also introduce novel behavioral analyses of the deliberation processes elicited by EdM challenge and use detailed multi-factorial explorations to reveal how these processes are impacted by age, temporal retention demand, difficulty of EdM challenge, and anticipation of trial outcome. Our observations indicate that deliberation requires remembering while accurate anticipation - in which a critical age-related deficit is also observed - requires active forgetting. Our results represent a significant advance towards unifying our understanding of the neurocognitive processes underpinning everyday-like memory, RIF, mnemonic deliberation, anticipatory function, and how they all are impacted by the physiological ageing process. In parallel, we present preliminary results using a transgenic mouse model which point to a fundamental role for the endocannabinoid system (eCS) in active forgetting and EdM, thereby demonstrating that deeper investigation of previously characterized age-related decline of the eCS should be a pre-clinical priority with a view to developing treatments for age-related decline of EdM function.

show abstract

“…In this study, we also con rmed a time-dependent change in both the electrophysiological and biochemical experiments, even though electrophysiological impairment occurred at an earlier time phase than molecule alteration in the hippocampus of the HCNP-pp KO mice when compared to that in the agematched control mice. Both an age-related cholinergic decline and GABAergic increase in the cell number were revealed in the MSN of rats at 22 months old, while the expression of the cholinergic receptor, α7 nicotine receptor, M1 receptor, GABA-a receptor, glutamatergic receptors, NMDAR subunit 2B (NR2B), and GluR1 in the hippocampus of rats was decreased with age [26,27] . A binding assay found that VAchT may also decrease in the hippocampus with age [28] .…”

Section: Discussionmentioning

confidence: 99%

Reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice

Suzuki

Ohi

Sato

et al. 2022

Preprint

View full text Add to dashboard Cite

Cholinergic activation can enhance glutamatergic activity in the hippocampus under pathologic conditions, such as Alzheimer’s disease and Lewy body disease. We aimed to elucidate the relationship between glutamatergic neural suppression and cholinergic neural dysfunction. We reported the importance of hippocampal cholinergic neurostimulating peptide (HCNP) in inducing acetylcholine synthesis in the MSN. Here, we demonstrated that HCNP-precursor protein (pp) knockout (KO) mice electrophysiologically presented with glutamatergic dysfunction in the hippocampus with age. The impairment of cholinergic dysfunction and the vesicular acetylcholine transporter decrease in the pre-synapse with reactive upregulation of the muscarinic M1 receptor may be partly involved in glutamatergic dysfunction in the hippocampus of HCNP-pp KO mice. These results in combination with our previous reports support the reduction of hippocampal theta power as region-specific in the stratum oriens of CA1 and a decrease in choline acetyltransferase and a direct reduction in acetylcholine in the hippocampus. This may support that HCNP-pp KO mice are an adequate genetic model for cholinergic functional impairment in septo-hippocampal interactions. Thus, according to cholinergic hypothesis this model mice might have a potential as a partial pathological animal model for Alzheimer’s disease.

show abstract

Age-related changes in medial septal cholinergic and GABAergic projection neurons and hippocampal neurotransmitter receptors: relationship with memory impairment

Cited by 8 publications

References 68 publications

Cellular and Molecular Changes During Aging in MEC: Unveiling the Role of Bglap3 Neurons in Cognitive Aging

Cellular and Molecular Changes During Aging in MEC: Unveiling the Role of Bglap3 Neurons in Cognitive Aging

To deliberate, remember; to anticipate, forget: Cognitive deliberation profiles underpinning active forgetting-dependent everyday-like memory performance in young and aged mice

Reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice

Contact Info

Product

Resources

About