Neuroscience Across Species

According to the chemical brain hypothesis, the evolution of the nervous system was preceded by systems based on chemical signaling, such as peptides. Placozoans are a group of nerveless, extremely simple marine animals that display characteristic, oscillatory, and partially social feeding behavior. During feeding, the animals rhythmically expand and shrink their bodies to digest prey and absorb nutrients, a process that is controlled by peptidergic signaling. They represent an ideal model for studying the early emergence of behavioral coordination, the mechanisms of neuropeptidergic action, and the evolution of social behaviors.

The goal of our project was to explore the molecular basis of foraging behavior, guided by the assumption that peptide-evoked oscillatory behavioral patterns in Placozoa are driven by oscillations in cytoplasmic calcium concentration. We also investigated inter-animal coordination of oscillatory behavior and established an artificial evolution paradigm aimed at tracking changes in oscillatory patterns as the animals adapt to different temperature conditions.

To that end, we applied automated behavioral assays, machine-learning–based behavioral analysis, pharmacological approaches, and electron microscopy imaging to investigate the relationship between cytoplasmic calcium levels and oscillatory properties, as well as to observe the molecular structures connecting animals during social foraging.

We show that interventions targeting ion channels and pumps that regulate calcium transport into and out of the cytoplasm induce changes in oscillatory patterns consistent with our hypotheses. We also demonstrate that animals foraging socially coordinate their behavior and provide evidence that membrane-based connections of unknown nature may contribute to this effect. Furthermore, we present the results of an artificial evolutionary process in which animals adapt to lower temperatures by altering their oscillatory patterns.

We demonstrate that Placozoans are a very useful model for studying the coordination of behaviour by chemical signals, including neuropeptides, the evolution of social behaviour and behavioural adaptation to changing environmental conditions.

Neurodegenerative diseases are chronic, progressive and incurable neurological illnesses. Emerging evidence suggests that their origins lie in a complex interplay between genetic and environmental factors. The latter are of growing importance as life expectancy and exposure of people increase. A putative causative agent is 2,4-diaminobutyric acid (DABA), a product of ubiquitous cyanobacteria, whose neurotoxic potential is insufficiently examined.

We therefore examine the electrophysiological effects of DABA on Retzius neurons.

Effects of increasing concentrations of DABA (1, 3, 5 and 10 mM) on electrical properties of leech neuron membrane were investigated using intracellular sharp electrode recordings.

Our results show that DABA elicits a strong excitatory effect on neurons, causing extensive membrane depolarization several times larger than that induced by glutamate and aspartate or environmental excitatory amino acids. At concentrations of 3 mM and higher, DABA induced a two-stage membrane depolarization, which is a novel excitatory phenomenon reported on our model. Depolarizing action of DABA is dependent on sodium ions and coupled with an increase of Retzius neuron membrane permeability. Blocking non-NMDA glutamate receptors with CNQX reduced the amplitude of the first stage, while inhibition of the transport system for neutral amino acids with L-Alanine markedly decreased the second stage of depolarization.

DABA produces substantial membrane depolarization, several times greater than that of other amino acids known for their excitatory effects, making it a potentially significant environmental factor in neurodegenerative diseases. This ubiquitous excitatory amino acid activates ionotropic glutamate receptors during the first stage and sodium-dependent transporters for neutral amino acids during the second stage of depolarization. These mechanisms initiate processes crucial for neurodegeneration – excitotoxicity, osmotic stress and energy depletion of neurons.

FINANCIAL SUPPORT: Ministry of Education, Science and Technological Development, project number 451-03-66/2025-03/200110

Maternal diet during gestation and lactation is increasingly recognized as a critical determinant of offspring neurodevelopmental outcomes. Importantly, Western diet (WD) exposure at this crucial period predisposes offspring to cognitive deficits and long-term developmental disorders.

The impact of maternal WD throughout pregnancy and lactation on offspring behavior and region and age-specific brain molecular dysregulation at certain postnatal days (PND).

Female Wistar rats were fed either a control diet (CD) or a high-fat (WD) throughout gestation and lactation (14 weeks total). After weaning, both male and female offspring were maintained on a CD and assessed at (PND) 30, 60, and 90. Behavioral screening included the open field, elevated zero maze, self-grooming, marble burying, and social interaction tests. Furthermore, molecular mechanisms were examined using RNA sequencing of the hippocampus (HIP) and prefrontal cortex (PFC), followed by protein-level validation of selected targets using ELISA.

Maternal WD exposure increased body weight and obesity in male offspring and induced significant behavioral alterations at early developmental stages. At PND30, male progeny subjected to WD demonstrated notable changes in locomotor activity, anxiety-related behaviors, grooming, and social interaction, distinguished by varying sex-specific patterns. Moreover, molecular analyses revealed that male WD-offspring displayed alterations in HIP, with EDN1 dysregulation at PND30, alongside changes in KLF2, AGTRAP, VEGF, and eNOS at PND60. Conversely, female offspring exposed to WD exhibited VEGF dysregulation at PND60 in the PFC and eNOS changes at both PND30 and PND60.

To sum up, the above findings indicate that maternal (WD) exposure induces early, sex-dependent behavioral dysregulation accompanied by molecular alterations in specific brain regions critical for cognition and social behavior, supporting the concept of it as a contributor to neurodevelopmental vulnerability.

FINANCIAL SUPPORT: by research grant UMO-2022/45/B/NZ4/03951 from the National Science Centre, Kraków, Poland (to M. Filip), and partially funded by the Maj Institute of Pharmacology, Polish Academy of Sciences.