scholarly journals Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Sonia Afroz ◽  
Julie Parato ◽  
Hui Shen ◽  
Sheryl Sue Smith
Keyword(s):  
Actin Cytoskeleton ◽  
Dendritic Spines ◽  
Gabaa Receptors ◽  
Pyramidal Cells ◽  
Spine Density ◽  
Inhibitory Receptor ◽  
Wild Type ◽  
Nmdar Activation ◽  
Cytoskeleton Remodeling ◽  
Synaptic Pruning

Adolescent synaptic pruning is thought to enable optimal cognition because it is disrupted in certain neuropathologies, yet the initiator of this process is unknown. One factor not yet considered is the α4βδ GABAA receptor (GABAR), an extrasynaptic inhibitory receptor which first emerges on dendritic spines at puberty in female mice. Here we show that α4βδ GABARs trigger adolescent pruning. Spine density of CA1 hippocampal pyramidal cells decreased by half post-pubertally in female wild-type but not α4 KO mice. This effect was associated with decreased expression of kalirin-7 (Kal7), a spine protein which controls actin cytoskeleton remodeling. Kal7 decreased at puberty as a result of reduced NMDAR activation due to α4βδ-mediated inhibition. In the absence of this inhibition, Kal7 expression was unchanged at puberty. In the unpruned condition, spatial re-learning was impaired. These data suggest that pubertal pruning requires α4βδ GABARs. In their absence, pruning is prevented and cognition is not optimal.

scholarly journals Effect of Phosphorylated Tau on Cortical Pyramidal Neuron Morphology during Hibernation

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Mamen Regalado-Reyes ◽  
Ruth Benavides-Piccione ◽  
Isabel Fernaud-Espinosa ◽  
Javier DeFelipe ◽  
Gonzalo León-Espinosa
Keyword(s):  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Morphological Changes ◽  
Brain Activity ◽  
Pyramidal Cells ◽  
Tau Hyperphosphorylation ◽  
Spine Density ◽  
Neuronal Structure ◽  
Morphological Alterations ◽  
Length And Area

Abstract The dendritic spines of pyramidal cells are the main postsynaptic target of excitatory glutamatergic synapses. Morphological alterations have been described in hippocampal dendritic spines during hibernation—a state of inactivity and metabolic depression that occurs via a transient neuronal tau hyperphosphorylation. Here, we have used the hibernating Syrian hamster to investigate the effect of hyperphosphorylated tau regarding neocortical neuronal structure. In particular, we examined layer Va pyramidal neurons. Our results indicate that hibernation does not promote significant changes in dendritic spine density. However, tau hyperphosphorylated neurons show a decrease in complexity, an increase in the tortuosity of the apical dendrites, and an increase in the diameter of the basal dendrites. Tau protein hyperphosphorylation and aggregation have been associated with loss or alterations of dendritic spines in neurodegenerative diseases, such as Alzheimer’s disease (AD). Our results may shed light on the correlation between tau hyperphosphorylation and the neuropathological processes in AD. Moreover, we observed changes in the length and area of the apical and basal dendritic spines during hibernation regardless of tau hyperphosphorylation. The morphological changes observed here also suggest region specificity, opening up debate about a possible relationship with the differential brain activity registered in these regions in previous studies.

scholarly journals Dendritic spines on GABAergic neurons respond to cholinergic signaling in theCaenorhabditis elegansmotor circuit

2019 ◽  
Author(s):  
Andrea Cuentas-Condori ◽  
Ben Mulcahy ◽  
Siwei He ◽  
Sierra Palumbos ◽  
Mei Zhen ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Motor Neurons ◽  
Dendritic Spines ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Live Cell ◽  
Spine Density ◽  
C Elegans ◽  
Cholinergic Signaling ◽  
Spine Morphogenesis

SUMMARYDendritic spines are specialized postsynaptic structures that detect and integrate presynaptic signals. The shape and number of dendritic spines are regulated by neural activity and correlated with learning and memory. Most studies of spine function have focused on the mammalian nervous system. However, spine-like protrusions have been previously reported in invertebrates, suggesting that the experimental advantages of smaller model organisms could be exploited to study the biology of dendritic spines. Here, we document the presence of dendritic spines inCaenorhabditis elegansmotor neurons. We used super-resolution microscopy, electron microscopy, live-cell imaging and genetic manipulation to show that GABAergic motor neurons display functional dendritic spines. Our analysis revealed salient features of dendritic spines: (1) A key role for the actin cytoskeleton in spine morphogenesis; (2) Postsynaptic receptor complexes at the tips of spines in close proximity to presynaptic active zones; (3) Localized postsynaptic calcium transients evoked by presynaptic activity; (4) The presence of endoplasmic reticulum and ribosomes; (5) The regulation of spine density by presynaptic activity. These studies provide a solid foundation for a new experimental paradigm that exploits the power ofC. elegansgenetics and live-cell imaging for fundamental studies of dendritic spine morphogenesis and function.HIGHLIGHTS-Spines inC. elegansGABAergic motor neurons are enriched in actin cytoskeleton.-Spines are dynamic structures.-Spines display Ca++transients coupled with presynaptic activation.-Spine density is regulated during development and is modulated by actin dynamics and cholinergic signaling.

scholarly journals Preventing adolescent synaptic pruning in mouse prelimbic cortex via local knockdown of α4βδ GABAA receptors increases anxiety response in adulthood

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew R. Evrard ◽  
Michael Li ◽  
Hui Shen ◽  
Sheryl S. Smith
Keyword(s):  
Gabaa Receptors ◽  
Adolescent Females ◽  
Prelimbic Cortex ◽  
Spine Density ◽  
Knock Out ◽  
Plus Maze ◽  
Anxiety Response ◽  
Global And Local ◽  
The Impact ◽  
Synaptic Pruning

AbstractAnxiety is increasingly reported, especially in adolescent females. The etiology is largely unknown, which limits effective treatment. Layer 5 prelimbic cortex (L5PL) increases anxiety responses but undergoes adolescent synaptic pruning, raising the question of the impact of pruning on anxiety. Here we show that preventing L5PL pruning increases anxiety in response to an aversive event in adolescent and adult female mice. Spine density of Golgi-stained neurons decreased ~ 63% from puberty (~ PND35, vaginal opening) to post-puberty (PND56, P < 0.0001). Expression of α4βδ GABAA receptors (GABARs) transiently increased tenfold in L5PL at puberty (P < 0.00001), but decreased post-pubertally. Both global and local knockdown of these receptors during puberty prevented pruning, increasing spine density post-pubertally (P < 0.0001), an effect reversed by blocking NMDA receptors (NMDARs). Pubertal expression of the NMDAR-dependent spine protein kalirin7 decreased (50%, P < 0.0001), an effect prevented by α4 knock-out, suggesting that α4βδ-induced reductions in kalirin7 underlie pruning. Increased spine density due to local α4 knockdown at puberty decreased open arm time on the elevated plus maze post-pubertally (62%, P < 0.0001) in response to an aversive stimulus, suggesting that increases in L5PL synapses increase anxiety responses. These findings suggest that prelimbic synaptic pruning is necessary to limit anxiety in adulthood and may suggest novel therapies.

Hormonal regulation of adult hippocampal dendritic spine density

1994 ◽  
Vol 52 ◽  
pp. 30-31
Author(s):  
Catherine S. Woolley ◽  
Bruce S. McEwen
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Hormonal Regulation ◽  
Dendritic Tree ◽  
Pyramidal Cells ◽  
Female Rat ◽  
Spine Density ◽  
Dendritic Spine Density ◽  
Progesterone Treatment ◽  
Lateral Branches

Dendritic spines cover the surface of a wide variety of neuronal types and are the postsynaptic sites of approximately 90% of the excitatory synapses formed in the central nervous system. Interestingly, changes in the morphology and/or density of dendritic spines have been shown to occur naturally, implying that they are a normal part of brain function. Even in the adult, dendritic spines are remarkably plastic. The hormonal state of an animal has been shown to be an important factor in regulation of dendritic spine density, both during development and in the adult.In the adult female rat, hippocampal CA1 pyramidal cells are particularly sensitive to variation in the circulating levels of the ovarian steroids, estradiol and progesterone. Removal of estradiol and progesterone by ovariectomy results in an approximately 50% decrease in the density of dendritic spines on the lateral branches of the apical dendritic tree. Treatment with estradiol can either protect against or reverse this decrease; subsequent progesterone treatment for as few as 5 hours significantly augments the effect of estradiol. By 18-24 hours following progesterone treatment, spine density returns to low values.

scholarly journals Effects of Aging on the Structure and Expression of NMDA Receptors of Somatostatin Expressing Neurons in the Mouse Hippocampus

2021 ◽  
Vol 13 ◽  
Author(s):  
Yaiza Gramuntell ◽  
Patrycja Klimczak ◽  
Simona Coviello ◽  
Marta Perez-Rando ◽  
Juan Nacher
Keyword(s):  
Cognitive Decline ◽  
Nmda Receptors ◽  
Dendritic Spines ◽  
Pyramidal Cells ◽  
Brain Structures ◽  
Inhibitory Neurons ◽  
Spine Density ◽  
Age Related ◽  
Effects Of Aging ◽  
The Impact

Changes in the physiology, neurochemistry and structure of neurons, particularly of their dendritic spines, are thought to be crucial players in age-related cognitive decline. One of the most studied brain structures affected by aging is the hippocampus, known to be involved in different essential cognitive processes. While the aging-associated quantitative changes in dendritic spines of hippocampal pyramidal cells have already been studied, the relationship between aging and the structural dynamics of hippocampal interneurons remains relatively unknown. Spines are not a frequent feature in cortical inhibitory neurons, but these postsynaptic structures are abundant in a subpopulation of somatostatin expressing interneurons, particularly in oriens-lacunosum moleculare (O-LM) cells in the hippocampal CA1. Previous studies from our laboratory have shown that the spines of these interneurons are highly plastic and influenced by NMDA receptor manipulation. Thus, in the present study, we have investigated the impact of aging on this interneuronal subpopulation. The analyses were performed in 3−, 9−, and 16-month-old GIN mice, a strain in which somatostatin positive interneurons express GFP. We studied the changes in the density of dendritic spines, en passant boutons, and the expression of NMDA receptors (GluN1 and GluN2B) using confocal microscopy and image analysis. We observed a significant decrease in dendritic spine density in 9-month-old animals when compared with 3-month-old animals. We also observed a decrease in the expression of the GluN2B subunit in O-LM cells, but not of that of GluN1, during aging. These results will constitute the basis for more advanced studies of the structure and connectivity of interneurons during aging and their contribution to cognitive decline.

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