During development, cortical plasticity is associated with the rearrangement of excitatory connections. While these connections become more stable with age, plasticity can still be induced in the adult cortex. Here we provide evidence that structural plasticity of inhibitory synapses onto pyramidal neurons is a major component of plasticity in the adult neocortex. In vivo two-photon imaging was used to monitor the formation and elimination of fluorescently labeled inhibitory structures on pyramidal neurons. We find that ocular dominance plasticity in the adult visual cortex is associated with rapid inhibitory synapse loss, especially of those present on dendritic spines. This occurs not only with monocular deprivation but also with subsequent restoration of binocular vision. We propose that in the adult visual cortex the experience-induced loss of inhibition may effectively strengthen specific visual inputs with limited need for rearranging the excitatory circuitry.

[5] are often localized far away from the soma, mitochondria are actively transported to these sites [6][7][8][9][10][11]. Also, the removal and degradation of mitochondria are tightly regulated [9,12,13], because dysfunctional mitochondria are a source of reactive oxygen species, which can damage the cell [14]. Deficits in mitochondrial trafficking have been proposed to contribute to the pathogenesis of Parkinson's disease, schizophrenia, amyotrophic lateral sclerosis, optic atrophy, and Alzheimer's disease [13,[15][16][17][18][19]. In neuronal cultures, about a third of mitochondria are motile, whereas the majority remains stationary for several days [8,20]. Activity-dependent mechanisms cause mitochondria to stop at synaptic sites [7,8,20,21], which affects synapse function and maintenance. Reducing mitochondrial content in dendrites decreases spine density [22,23], whereas increasing mitochondrial content or activity increases it [7]. These bidirectional interactions between synaptic activity and mitochondrial trafficking suggest that mitochondria may regulate synaptic plasticity. Here we investigated the dynamics of mitochondria in relation to axonal boutons of neocortical pyramidal neurons for the first time in vivo. We find that under these circumstances practically all mitochondria are stationary, both during development and in adulthood. In adult visual cortex, mitochondria are preferentially localized at putative boutons, where they remain for several days. Retinal-lesion-induced cortical plasticity increases turnover of putative boutons but leaves mitochondrial turnover unaffected. We conclude that in visual cortex in vivo, mitochondria are less dynamic than in vitro, and that structural plasticity does not affect mitochondrial dynamics. RESULTS AND DISCUSSION Few Motile Mitochondria in Axons of Pyramidal Neurons in Visual Cortex In VivoTo fluorescently label mitochondria and the neuronal structures in which they are localized, we performed in utero electroporation with two DNA constructs driving expression of mitomTurquoise2 and membrane-associated YFP. A cranial window was implanted once mice had reached the age of 8-10 weeks. This allowed us to visualize mitochondria in axonal arbors of layer 2/3 pyramidal neurons in V1 in vivo using two-photon microscopy (Figures 1A-1C; Movie S1). Two to three weeks after cranial window implantation, optical imaging of intrinsic imaging was performed to localize monocular V1. One week later, axonal branches in layer 1 and upper layer 2 were imaged using in vivo two-photon microscopy. We found that the density of mitochondria was 0.09 per mm ( Figure 1D). Surprisingly, the fraction of axonal mitochondria that were motile was only 0.83% ( Figure 1E), much lower than the 10%-30% previously observed in neuronal cultures [6][7][8][9][10]. We therefore asked whether the difference in mitochondrial motility was caused by the different experimental condition (in vivo versus in vitro) or by the difference in the age of the imaged neurons. We assessed mitochondrial motilit...

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The 5-HT3 receptor is a ligand-gated ion channel expressed on interneurons throughout the brain. So far, analysis of the 5-HT3A knockout mouse revealed changes in nociceptive processing and a reduction in anxiety related behavior. Recently, it was shown that the 5-HT3 receptor is also expressed on Cajal-Retzius cells which play a key role in cortical development and that knockout mice lacking this receptor showed aberrant growth of the dendritic tree of cortical layer II/III pyramidal neurons. Other mouse models in which serotonergic signaling was disrupted during development showed similar morphological changes in the cortex, and in addition, also deficits in social behavior. Here, we subjected male and female 5-HT3A knockout mice and their non-transgenic littermates to several tests of social behavior. We found that 5-HT3A knockout mice display impaired social communication in the social transmission of food preference task. Interestingly, we showed that in the social interaction test only female 5-HT3A knockout mice spent less time in reciprocal social interaction starting after 5 min of testing. Moreover, we observed differences in preference for social novelty for male and female 5-HT3A knockout mice during the social approach test. However, no changes in olfaction, exploratory activity and anxiety were detected. These results indicate that the 5-HT3A knockout mouse displays impaired social behavior with specific changes in males and females, reminiscent to other mouse models in which serotonergic signaling is disturbed in the developing brain.

Maternal licking and grooming (LG) exerts profound influence on hippocampal development and function in the offspring. However, little information is available on the effects of variations in maternal care on other brain regions. Here we examined the effects of variation in the frequency of maternal LG on morphological and electrophysiological properties of layer 2/3 pyramidal neurons in the somatosensory cortex in adult offspring. Compared to low LG offspring, high LG offspring displayed decreased dendritic complexity, reduced spine density and decreased amplitude of spontaneous postsynaptic currents. These changes were accompanied by higher levels of reelin expression in offspring of high LG mothers. Taken together, these findings suggest that differential amount of naturally-occurring variations in maternal LG is associated with enduring changes in dendritic morphology and synaptic function in layer 2/3 pyramidal neurons of the somatosensory cortex.

In various species and areas of the cerebral cortex, apical dendrites of pyramidal neurons form clusters which extend through several layers of the cortex also known as dendritic bundles. Previously, it has been shown that 5-HT3A receptor knockout mice show hypercomplex apical dendrites of cortical layer 2/3 pyramidal neurons, together with a reduction in reelin levels, a glycoprotein involved in cortical development. Other studies showed that in the mouse presubicular cortex, reelin is involved in the formation of modular structures. Here, we compare apical dendrite bundling in the somatosensory cortex of wildtype and 5-HT3A receptor knockout mice. Using a microtubule associated protein-2 immunostaining to visualize apical dendrites of pyramidal neurons, we compared dendritic bundle properties of wildtype and 5-HT3A receptor knockout mice in tangential sections of the somatosensory cortex. A Voronoi tessellation was performed on immunostained tangential sections to determine the spatial organization of dendrites and to define dendritic bundles. In 5-HT3A receptor knockout mice, dendritic bundle surface was larger compared to wildtype mice, while the number and distribution of reelin-secreting Cajal–Retzius cells was similar for both groups. Together with previously observed differences in dendritic complexity of cortical layer 2/3 pyramidal neurons and cortical reelin levels, these results suggest an important role for the 5-HT3 receptor in determining the spatial organization of cortical connectivity in the mouse somatosensory cortex.

<b><i>Background:</i></b> In this article, we present an evaluation of online psychoactive substance trade via Telegram, a free encrypted social media messenger service. The evaluation took place during the COVID-19 pandemic, which allowed us to monitor the effects of the spring 2020 lockdown in the Netherlands on substance trade via Telegram. <b><i>Objective:</i></b> The objective of this study was to evaluate whether changes in psychoactive substance trade on Telegram markets in the Netherlands can be observed during the COVID-19 pandemic. <b><i>Results:</i></b> Between December 2, 2019, and June 29, 2020, a total of 70,226 posts appeared in two analyzed Telegram groups. A total of 5,643 posts were psychoactive substance related. Based on the analyzed posts, Telegram is mostly a ‘“sellers” market as only a minority of the posts (6.3%) could be identified as a request for a substance. The proportion of posts related to specific substances varied between the periods before, during, and after the lockdown. The proportion of posts on the stimulants ecstasy, cocaine, and amphetamine was lower during the lockdown than before and after. For psychedelics – ketamine, lysergic acid diethylamide (LSD), and 2,5-dimethoxy-4-bromophenethylamine (2C-B) – and other substances, there was a relative increase in the number of posts during the lockdown, which was maintained after the lockdown. <b><i>Conclusions:</i></b> Telegram analysis shows that in the Netherlands, online psychoactive substance trade may have been affected during the COVID-19 pandemic. The direction of this effect was different for different classes of substances.