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Rollenhagen, A.

Publications and source records attributed to Rollenhagen, A..

5 recordsLinked to original sources

Astrocytes control oxytocin-based maternal behavior via connexin 30

Prosocial and affiliative behaviors rely on complex neuroendocrine neuronal circuits. Dynamic neuroglial interactions play prominent roles in shaping synaptic networks, whose alterations contribute to psychiatric disorders associated with social deficits. However, a role for astrocytes in regulating maternal behavior remains elusive. Here we show that female mice exhibiting increased oxytocin levels in the hypothalamic supraoptic nucleus upon social interactions with pups display neuroglial structural plasticity and downregulation of astroglial connexin 30, a protein involved in morphological remodeling. We found that impairing astroglial connexin 30 expression alters the structural properties of astrocytes by decreasing their volume and coverage of oxytocinergic synapses in the supraoptic nucleus of female mice. This functionally sets levels of plasma oxytocin and maternal behavior, exacerbating maternal care in virgin pup-naive female mice deficient for astroglial Cx30. Hypothalamic astrocytes, via connexin 30, are thus key determinants of oxytocin-based maternal behavior, whose alteration is known to impair social skills development in offspring.

neuroscience↗

Ultrastructural sublaminar-specific diversity of excitatory synaptic boutons in layer 1 of the adult human temporal lobe neocortex

Layer (L)1, beside receiving massive cortico-cortical, commissural and associational projections, is the termination zone of tufted dendrites of pyramidal neurons and the area of Ca2+ spike initiation. However, its synaptic organization in humans is not known. Quantitative 3D-models of excitatory synaptic boutons (SBs) in layer 1 of the human temporal lobe neocortex were generated from neocortical biopsy tissue using transmission electron microscopy, 3D-volume reconstructions and TEM tomography. Particularly, the size of active zones (AZs) and the readily releasable, recycling and resting pool of synaptic vesicles (SVs) were quantified. The majority of excitatory SBs contained numerous mitochondria comprising [~]7% of the total volume, had a large macular, non-perforated AZ ([~]0.20 {micro}m2) and were predominantly located on dendritic spines. Excitatory SBs had a total pool of [~]3500 SVs, a relatively large readily releasable ([~]4 SVs), recycling ([~]470 SVs) and resting ([~]2900 SVs) pool. Astrocytic coverage of excitatory SBs suggests both synaptic cross talk or removal of spilled glutamate by astrocytic processes at synaptic complexes. The structural composition of SBs in L1 may underlie the function of L1 networks that mediate, integrate and synchronize contextual and cross-modal information, enabling flexible and state-dependent processing of feedforward sensory inputs from other layers of the cortical column.

neuroscience↗

Physiological synaptic activity and recognition memory are fueled by astroglial glutamine

Presynaptic glutamate replenishment is fundamental to brain function. In high activity regimes, such as epileptic episodes, this process is thought to rely on the glutamate-glutamine cycle between neurons and astrocytes. However the presence of an astroglial glutamine supply, as well as its functional relevance in vivo in the healthy brain remain controversial, partly due to a lack of tools that can directly examine glutamine transfer. Here, we generated a novel fluorescent probe that tracks glutamine in live cells, which provided direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions. This mobilization is mediated by connexin43, an astroglial protein with both gap-junction and hemichannel functions, and is essential for synaptic transmission and object recognition memory. Our findings uncover an indispensable recruitment of astroglial glutamine in physiological synaptic activity and memory via an unconventional pathway, thus providing an astrocyte basis for cognitive processes.

neuroscience↗

Area-specific synapse structure in branched axons reveals a subcellular level of complexity in thalamocortical networks

Thalamocortical Posterior nucleus (Po) axons innervating the somatosensory (S1) and motor (MC) vibrissal cortices are key links in the brain neuronal network that allows rodents to explore the environment whisking with their motile vibrissae. Here, using high-end 3D electron microscopy, we demonstrate massive differences between MC vs. S1 Po synapses in a) bouton and active zone size; b) neurotransmitter vesicle pool size; c) mitochondria distribution near synapses; and d) proportion of non-spinous dendrite contacts. These differences are as large, or bigger, than those between Po and ventroposterior thalamic nucleus synapses in S1. Moreover, using single-axon transfection labeling, we show that the structure of boutons in the MC vs. S1 branches of individual Po axons is different. These structural differences parallel striking, recently-discovered divergences in functional efficacy and plasticity between S1 and MC Po synapses, and overall reveal a new, subcellular level of thalamocortical circuit complexity, unaccounted for in current models.

neuroscience↗

Ultrastructural heterogeneity of human layer 4 excitatory synaptic boutons in the adult temporal lobe neocortex

Synapses are fundamental building blocks that control and modulate the behavior of brain networks. How their structural composition, most notably their quantitative morphology underlies their computational properties remains rather unclear, particularly in humans. Here, excitatory synaptic boutons (SBs) in layer 4 (L4) of the temporal lobe neocortex (TLN) were quantitatively investigated.\n\nBiopsies from epilepsy surgery were used for fine-scale and tomographic electron microscopy to generate 3D-reconstructions of SBs. Particularly, the size of active zones (AZs) and of the three functionally defined pools of synaptic vesicles (SVs) were quantified.\n\nSBs were comparably small ([~]2.50 m2), with a single AZ ([~]0.13 {micro}m2) and preferentially established on spines. SBs had a total pool of [~]1800SVs with strikingly large readily releasable ([~] 20), recycling ([~] 80) and resting pools ([~]850).\n\nThus, human L4 SBs may act as amplifiers of signals from the sensory periphery and integrate, synchronize and modulate intra- and extra-cortical synaptic activity.

neuroscience↗