Biology subjects

Jager, P.

Publications and source records attributed to Jager, P..

5 recordsLinked to original sources

bioRxiv2026

Prenatal stress interacts with embryonic loss of Fgfr2 to increase locomotor hyperactivity in mice

Attention-deficit/hyperactivity disorder (ADHD) is a developmental psychiatric disorder associated with a complex interplay of genetic and environmental risk factors. We have shown embryonic dorsal forebrain loss in mice of fibroblast growth factor receptor 2 (Fgfr2), which has a critical role in normal brain development, results in ADHD-relevant phenotypes: increased locomotion and sociability, and impaired working memory postnatally. How such genetic vulnerabilities interact with environmental exposures to translationally model human ADHD risk remains unclear. Here, we pair the embryonic hGFAP-cre Fgfr2 conditional knockout (Fgfr2 cKO) mouse model with prenatal repetitive restraint stress, modeling an environmental factor associated with ADHD risk, to assess adult offspring behaviors and dopamine transporter (DAT) levels. Offspring of prenatally stressed, Fgfr2 cKO mice show increased locomotion (80% compared to non-stressed, Fgfr2 cKO animals). Prenatal stress led to a trend increase in impulsivity and trend decrease in working memory but did not affect sociability. There were no interactions with Fgfr2 cKO observed in these behaviors. Neurobiologically, prenatal stress led to a trend decrease in medial frontal cortex DAT, but these changes did not correlate with behavior. Taken together, our findings implicate prenatal stress as a potential contributor to gene-environment interactions for ADHD risk, supporting its use in translational animal models of childhood psychiatric disorders.

neuroscience↗

bioRxiv2024

Phylogenomics, Classification, and Lifestyle Evolution in Raft- and Nursery web- Spiders (Araneae: Dolomedidae and Pisauridae)

Pisauridae Simon, 1890 or "nursery web spiders" are a global and heterogenous assemblage of spider genera with diverse lifestyles, containing web builders and webless species, as well as terrestrial and semi-aquatic species, notably "fishing spiders", genus Dolomedes Latreille, 1804. Incomplete, unresolved, or conflicting phylogenies have so far hampered testing for Dolomedes and pisaurid monophyly and evolution. Here, we broadly address these questions within a phylogenomic and comparative framework. Our goals are i) reconstruction of a robust phylogeny to test the monophyly of Dolomedes and Pisauridae and to amend Dolomedes classification; ii) estimation of evolutionary shifts and trends in lifestyles and capture webs; and iii) evaluation of hypotheses of morphological trait association with a semi-aquatic lifestyle. To this end we generate subgenomic data (ultraconserved elements or UCE) for 53 Dolomedes species and 28 pisaurid genera. We analyze these data using maximum likelihood, Bayesian, and multi-species coalescence approaches, as well as using two different phylogenetic time calibration methods, RelTime and MCMCtree. Consistent across analytical approaches, our phylogenies reject the monophyly of both Pisauridae and Dolomedes. "Pisaurid" genera fall into three clades: 1) Focal Clade I groups the majority, including Pisaura Simon, 1886, hence representing true pisaurids; 2) Focal Clade II = Blandinia Tonini et al., 2016 is sister to Trechaleidae Simon, 1890 and Lycosidae Sundevall, 1833; 3) Focal Clade III with fishing and raft spiders groups Dolomedes, Megadolomedes Davies and Raven, 1980, and Ornodolomedes Raven and Hebron, 2018 and is sister to Focal Clade II, Trechaleidae, and Lycosidae. Our taxonomy, based on complementary taxa and morphological evidence, resurrects Dolomedidae Simon, 1876 to include Dolomedes and the Oceanic genera Bradystichus Simon, 1884, Megadolomedes, Caledomedes Raven and Hebron, 2018, Mangromedes Raven and Hebron, 2018, Ornodolomedes, and Tasmomedes Raven and Hebron, 2018. Both RelTime and MCMCtree analyses yield comparable divergence estimations: Pisauridae origin is estimated between 29 and 40 Ma; Blandinia between 21 and 34 Ma; Dolomedidae between 10 and 17 Ma; and Dolomedes between 9 and 16 Ma. In order to avoid misleading significant correlations and/or over-resolved ancestral states, we performed taxon sampling bias correction in all evolutionary analyses. Evolutionary analyses reconstruct semi-aquatic lifestyle as ancestral to a large clade containing pisaurids, lycosids, trechaleids, Blandinia, and dolomedids, with several reversals to terrestrial lifestyle. Capture webs evolved at least three times, with reversals. Counter to expectation, the evolution of lifestyles and capture webs are independent. Although leg and tarsus lengths do not indicate lifestyles, semi-aquatic taxa are significantly larger than terrestrial ones. We explain this pattern with a biomechanical threshold over which surface tension can be broken while spiders forage under water. Our time-calibrated analyses indicate that the evolution of terrestrial and web-building lifestyles from semi-aquatic ancestors in Pisauridae coincided with cooling and drying climates in the mid-Miocene. We therefore hypothesize that climatic changes have acted as strong selection pressures toward lifestyle diversification.

evolutionary biology↗

bioRxiv2024

The type of inhibition provided by thalamic interneurons alters the input selectivity of thalamocortical neurons.

A fundamental problem in neuroscience is how neurons select for their many inputs. A common assumption is that a neurons selectivity is largely explained by differences in excitatory synaptic input weightings. Here we describe another solution to this important problem. We show that within the first order visual thalamus, the type of inhibition provided by thalamic interneurons has the potential to alter the input selectivity of thalamocortical neurons. To do this, we developed conductance injection protocols to compare how different types of synchronous and asynchronous GABA release influence thalamocortical excitability in response to realistic patterns of retinal ganglion cell input. We show that the asynchronous GABA release associated with tonic inhibition is particularly efficient at maintaining information content, ensuring that thalamocortical neurons can distinguish between their inputs. We propose a model where alterations in GABA release properties results in rapid changes in input selectivity without requiring structural changes in the network.

neuroscience↗

bioRxiv2022

A role for thalamic projection GABAergic neurons in circadian responses to light

The thalamus is an important hub for sensory information and participates in sensory perception, regulation of attention, arousal and sleep. These functions are executed primarily by glutamatergic thalamocortical neurons that extend axons to the cortex and initiate cortico-thalamocortical connectional loops. However, the thalamus also contains projection GABAergic neurons that do not engage in direct communication with the cortex. Here, we have harnessed recent insight into the development of the intergeniculate (IGL), the ventrolateral geniculate (LGv) and the perihabenula (pHB) to specifically target and manipulate thalamic projection GABAergic neurons in female and male mice. Our results show that thalamic GABAergic neurons of the IGL and LGv receive retinal input from diverse classes of ipRGCs, but not from the M1 ipRGC type, while those in the pHB lack direct retinal input. We describe the synergistic role of the photoreceptor melanopsin and the thalamic neurons of the IGL/LGv in circadian entrainment to dim light. We identify a requirement for the thalamic IGL/LGv in the rapid changes in vigilance states associated with circadian light transitions. Furthermore, we map a previously undescribed thalamic network of developmentally related GABAergic neurons in the IGL/LGv complex and the pHB potentially involved in light-dependent mood regulation. Significance statementThe intergeniculate leaflet and ventral geniculate nucleus are part of the extended circadian system and mediate some non-image-forming visual functions. Here we show that each of these structures has a thalamic (dorsal) as well as prethalamic (ventral) developmental origin. We map the retinal input to thalamus-derived cells in the IGL/LGv complex and discover that while ipRGC input is dominant, this is not likely to originate from M1-ipRGCs. We describe the extent of similarity in synaptic input to developmentally related cells in the IGL/LGv and in the perihabenula nucleus (pHB). We implicate thalamic cells in the IGL/LGv in vigilance state transitions at circadian light changes and in overt behavioural entrainment to dim light, the latter exacerbated by concomitant loss of melanopsin expression.

neuroscience↗

bioRxiv2019

Inhibitory interneurons distribute widely across the mouse thalamus and form ontogenetic spatial clusters

The proportion and distribution of local inhibitory neurons (interneurons) in the thalamus varies widely across mammals. The ubiquitous presence of interneurons in the thalamus of primates contrasts with the extreme sparsity of interneurons reported in mice and other small-brained mammals. This is reflected in the structure and function of thalamic local circuits, which are more complex in primates compared to rodents. To what extent the broad range of interneuron densities observed in mammalian species reflect the appearance of novel interneuron types or the elaboration of a plesiomorphic ontogenetic program, remains unclear. Here, we identify a larger than expected complexity and distribution of interneurons across the mouse thalamus, where all thalamic interneurons can be traced back to two developmental programs: one specified in the midbrain and the other in the forebrain. Interneurons migrate to functionally distinct thalamocortical nuclei depending on their origin the abundant, midbrain-derived class populates the first and higher order sensory thalamus while the rarer, forebrain-generated class is restricted to some higher order associative regions. We also observe that markers for the midbrain-born class are abundantly expressed throughout the thalamus of the New World monkey marmoset. These data therefore reveal that, despite the broad variability in interneuron density across mammalian species, the blueprint of the ontogenetic organization of thalamic interneurons of larger-brained mammals exists and can be studied in mice.

neuroscience↗