Lifelong Impact of Variations in Maternal Care on Dendritic Structure and Function of Cortical Layer 2/3 Pyramidal Neurons in Rat Offspring

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

Impaired Social Behavior in 5-HT3A Receptor Knockout Mice

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

Alterations in Apical Dendrite Bundling in the Somatosensory Cortex of 5-HT3A Receptor Knockout Mice

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

Maternal LG affects the amplitude of spontaneous postsynaptic currents in cortical layer 2/3 pyramidal neurons.

<p>(<i>A,B</i>) Typical examples of evoked action potentials <i>(A</i>) and recordings of spontaneous postsynaptic currents <i>(B</i>) obtained from layer 2/3 pyramidal neurons in the somatosensory cortex of male adult high and low LG rats. (<i>C,D</i>) Normalized cumulative frequency (<i>C</i>) and cumulative amplitude <i>(D</i>) of spontaneous events recorded from layer 2/3 pyramidal neurons. The amplitude distribution of high LG rats is shifted leftwards as compared to low LG rats (p<0.01, Kolgomorov-Smirnov test), whereas the frequency distributions do not differ significantly.</p

Differential reelin levels in the cortex of adult high and low LG rats.

<p>(<i>A</i>) Western blots immunoprobed for reelin with three bands at 450, 370 and 180 kDA corresponding to the full length and truncated reelin fragments in high and low LG rats. (<i>B</i>) Reelin immunoreactivity expressed as a ratio in optical density for reelin/ β actin for the accumulative reelin bands from high LG and low LG rats. Data are expressed as the mean±SEM. Asterisks indicate significant differences (* p<0.05).</p

Maternal LG has an effect on various components of the dendritic complexity index.

<p>To calculate the dendritic complexity index for the apical and basal dendrites of cortical layer 2/3 pyramidal neurons of high LG and low LG rats total arbor length, branch tip order, branch tip number and primary dendrite number were analyzed. Data are expressed as the mean±SEM. Asterisks indicate significant differences (* p<0.05, ** p<0.01).</p

Cannabis adulterated with the synthetic cannabinoid receptor agonist MDMB-4en-PINACA and the role of European drug checking services.

BackgroundEuropean drug checking services exchange information on drug trends within the Trans European Drug Information (TEDI) network, allowing monitoring and coordination of responses. Starting in Spring 2020, several services detected the synthetic cannabinoid receptor agonist MDMB-4en-PINACA in adulterated low-THC cannabis products.MethodsCannabis products suspected of adulteration were analyzed for the presence of MDMB-4en-PINACA by 9 services in 8 countries within the TEDI network. If available, phytocannabinoid analysis was also performed.Results1142 samples sold as cannabis in herbal, resin and e-liquid form were analyzed, of which 270 were found to contain MDMB-4en-PINACA. All cannabis samples contained low THC (ConclusionAdulteration of cannabis with synthetic cannabinoid receptor agonists is a new phenomenon that carries risk for people who use it. Given that cannabis consumers are not a usual target group for drug checking services, services and associated harm reduction interventions could be reconfigured to include them