Activity-Induced Nr4a1 Regulates Spine Density and Distribution Pattern of Excitatory Synapses in Pyramidal Neurons

Three-dimensional (3D) reconstruction from electron microscopy (EM) datasets is a widely used tool that has improved our knowledge of synapse ultrastructure and organization in the brain. Rearrangements of synapse structure following maturation and in synaptic plasticity have been broadly described and, in many cases, the defective architecture of the synapse has been associated to functional impairments. It is therefore important, when studying brain connectivity, to map these rearrangements with the highest accuracy possible, considering the affordability of the different EM approaches to provide solid and reliable data about the structure of such a small complex. The aim of this work is to compare quantitative data from two dimensional (2D) and 3D EM of mouse hippocampal CA1 (apical dendrites), to define whether the results from the two approaches are consistent. We examined asymmetric excitatory synapses focusing on post synaptic density and dendritic spine area and volume as well as spine density, and we compared the results obtained with the two methods. The consistency between the 2D and 3D results questions the need—for many applications—of using volumetric datasets (costly and time consuming in terms of both acquisition and analysis), with respect to the more accessible measurements from 2D EM projections.

Download Full-text

Kalirin-7 is a Key Player in the Formation of Excitatory Synapses in Hippocampal Neurons

The Scientific World JOURNAL ◽

10.1100/tsw.2010.148 ◽

2010 ◽

Vol 10 ◽

pp. 1655-1666 ◽

Cited By ~ 9

Author(s):

Xin-Ming Ma

Keyword(s):

Hippocampal Neurons ◽

Pyramidal Neurons ◽

Synapse Formation ◽

Pdz Domain ◽

Long Term Potentiation ◽

Binding Motif ◽

Excitatory Synapses ◽

Spine Density ◽

Chronic Cocaine ◽

And Function

Kalirin-7 (Kal7), a major isoform of Kalirin in the adult rodent hippocampus, is exclusively localized to the postsynaptic side of mature excitatory synapses in hippocampal neurons. Kal7 interacts with multiple PDZ domain—containing proteins through its unique PDZ binding motif. Overexpression of Kal7 increases spine density and spine size, whereas reduction of endogenous Kal7 expression by small hairpin RNA (shRNA) causes a decrease in synapse number and spine density in cultured hippocampal neurons. Hippocampal CA1 pyramidal neurons of Kal7 knockout (Kal7KO) mice show decreased spine density, spine length, synapse number, and postsynaptic density (PSD) size in their apical dendrites; are deficient in long-term potentiation (LTP); and exhibit decreased frequency of spontaneous excitatory postsynaptic current (sEPSC). Kal7 plays a key role in estrogen-mediated spine/synapse formation in hippocampal neurons. Kal7 is also an essential determinant of dendritic spine formation following chronic cocaine treatment. Kal7 plays a key role in excitatory synapse formation and function.

Download Full-text

Dendritic Spine Density of Pyramidal Neurons in Field CA1 of the Hippocampus Decreases due to Chronic Tryptophan Restriction

Nutritional Neuroscience ◽

10.1080/1028415x.1998.11747233 ◽

1998 ◽

Vol 1 (3) ◽

pp. 237-242 ◽

Cited By ~ 6

Author(s):

M.I. Pérez-Vega ◽

G. Barajas-López ◽

A.R. del Angel-Meza ◽

I. González-Burgos ◽

A. Feria-Velasco

Keyword(s):

Dendritic Spine ◽

Pyramidal Neurons ◽

Spine Density ◽

Dendritic Spine Density ◽

Field Ca1

Download Full-text

Lack of change in CA1 dendritic spine density or clustering in rats following training on a radial-arm maze task

Wellcome Open Research ◽

10.12688/wellcomeopenres.15745.2 ◽

2020 ◽

Vol 5 ◽

pp. 68

Author(s):

Emma Craig ◽

Christopher M. Dillingham ◽

Michal M. Milczarek ◽

Heather M. Phillips ◽

Moira Davies ◽

...

Keyword(s):

Dendritic Spines ◽

Pyramidal Neurons ◽

Memory Load ◽

Spatial Location ◽

Memory Formation ◽

Spatial Task ◽

Radial Arm Maze ◽

Nearest Neighbour ◽

Spine Density ◽

Ca1 Region

Background: Neuronal plasticity is thought to underlie learning and memory formation. The density of dendritic spines in the CA1 region of the hippocampus has been repeatedly linked to mnemonic processes. Both the number and spatial location of the spines, in terms of proximity to nearest neighbour, have been implicated in memory formation. To examine how spatial training impacts synaptic structure in the hippocampus, Lister-Hooded rats were trained on a hippocampal-dependent spatial task in the radial-arm maze. Methods: One group of rats were trained on a hippocampal-dependent spatial task in the radial arm maze. Two further control groups were included: a yoked group which received the same sensorimotor stimulation in the radial-maze but without a memory load, and home-cage controls. At the end of behavioural training, the brains underwent Golgi staining. Spines on CA1 pyramidal neuron dendrites were imaged and quantitatively assessed to provide measures of density and distance from nearest neighbour. Results: There was no difference across behavioural groups either in terms of spine density or in the clustering of dendritic spines. Conclusions: Spatial learning is not always accompanied by changes in either the density or clustering of dendritic spines on the basal arbour of CA1 pyramidal neurons when assessed using Golgi imaging.

Download Full-text

Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons

10.1101/2020.12.10.419507 ◽

2020 ◽

Author(s):

Lauren Tereshko ◽

Ya Gao ◽

Brian A. Cary ◽

Gina G. Turrigiano ◽

Piali Sengupta

Keyword(s):

Primary Cilia ◽

Neuronal Development ◽

Pyramidal Neurons ◽

Somatostatin Receptor ◽

Cognitive Disorders ◽

Mammalian Brain ◽

Excitatory Synapses ◽

Ciliary Signaling ◽

Neocortical Pyramidal Neurons

ABSTRACTPrimary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured neocortical pyramidal neurons, and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to pyramidal neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses, and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.

Download Full-text

Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling

10.1101/065391 ◽

2016 ◽

Author(s):

Tharkika Nagendran ◽

Rylan S. Larsen ◽

Rebecca L. Bigler ◽

Shawn B. Frost ◽

Benjamin D. Philpot ◽

...

Keyword(s):

Dendritic Spines ◽

Dendritic Spine ◽

Pyramidal Neurons ◽

Spine Density ◽

Axon Injury ◽

Synaptic Remodeling ◽

Nerve Tracts ◽

Specific Increase ◽

Microfluidic Chambers

AbstractInjury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription. Similarly, directly injured corticospinal neurons in vivo also exhibit a specific increase in spiking following axon injury. Axotomy-induced hyper-excitability of cultured neurons coincides with elimination of inhibitory inputs onto injured neurons, including those formed onto dendritic spines. Netrin-1 downregulation occurs following axon injury and exogenous netrin-1 applied after injury normalizes spine density, presynaptic excitability, and inhibitory inputs at injured neurons. Our findings show that intrinsic signaling within damaged neurons regulates synaptic remodeling and involves netrin-1 signaling.

Download Full-text