The research, published in eNeuro, an open-access, peer-reviewed scientific journal published by the Society for Neuroscience, explores how nicotine influences key areas associated with reward and aversion, showcasing a nuanced relationship that varies based on dosage, sex and distinct brain regions. The medial habenula (MHb), a region known for regulating nicotine aversion, takes center stage in the study. Researchers discovered that MHb activity experiences fluctuations, either heightened or diminished, depending on factors such as the amount of nicotine consumed, dosage variations (with or without menthol), and the sex of the subject. Intriguingly, this modulation was not mirrored in reward centers like the ventral tegmental area, challenging previous assumptions about nicotine’s impact.

“This study demonstrates that the activity of crucial brain regions associated with nicotine dependence is altered in different ways based on nicotine dosage and sex,” said lead researcher Nathan Olszewski, a biomedical research doctoral student at Marshall University in the laboratory of Brandon J. Henderson, Ph.D. “Nicotine usage affects individuals uniquely, making it advisable for users to exercise caution.”

The study employed a vapor-inhalation model of nicotine self-administration in mice, utilizing nose poking to earn nicotine vapor deliveries. Employing patch-clamp electrophysiology, researchers elucidated changes in neuronal excitability in the medial habenula and ventral tegmental area based on nicotine dosage and sex. Fast-scan cyclic voltammetry was also used to assess changes in dopamine release dynamics in the nucleus accumbens.

“In our field, attention has predominantly focused on specific regions like the ventral tegmental area,” said Henderson, an associate professor of biomedical sciences at Marshall University. “This study underscores the necessity of exploring other brain areas controlling the negative aspects of nicotine exposure.”

The researchers aim to expand their investigation to other brain regions, particularly focusing on the interplay between the MHb and the interpeduncular nucleus (IPN). This circuit, known as the aversive pathway of nicotine usage, plays a crucial role in limiting nicotine intake and withdrawal symptoms. Future research will utilize electrophysiology, confocal microscopy and RNA-fluorescent in situ hybridization (FISH) to understand how nicotine alters the activity and expression of nicotinic acetylcholine receptors in this aversive circuit.

In addition to Olszewski and Henderson, Samuel Tetteh-Quarshie, another Ph.D. student in the Henderson laboratory, is a co-author on the study. This study was supported with grant funding (#DA050717 to Henderson) from the National Institute on Drug Abuse (NIDA).

Visible Changes in the Nervous System

A research team from Julius-Maximilians-Universität Würzburg (JMU) discovered this a few years ago. However, it was previously unknown where in the ants’ brains the magnetic information is processed. This has now changed: In a new study published in the journal PNAS — Proceedings of the National Academy of Sciences, the team shows that information about the Earth’s magnetic field is primarily processed in the ants’ internal compass, the so-called central complex, and in the mushroom bodies, the animals’ learning and memory centers.

Professor Wolfgang Rössler, holder of the Chair of Behavioral Physiology and Sociobiology at the University of Würzburg, Dr. Pauline Fleischmann, former scientist at the Chair of Behavioral Physiology and Sociobiology and now a member of the Neurosensorics/ Animal Navigation working group at the University of Oldenburg, and Dr. Robin Grob, who has since moved from Rössler’s chair to the Norwegian University of Science and Technology in Trondheim, were responsible for this study.

First Exploratory Walks for Calibration

“Before an ant leaves its underground nest for the first time and goes in search of food, it has to calibrate its navigation system,” says Pauline Fleischmann, explaining the background to the work. During so-called learning walks, the animals then explore the immediate surroundings around the nest entrance and repeatedly pirouette around their own body axis with short stops in between. During these pauses, they always look exactly back in the direction of the nest entrance, even though they cannot see it — a tiny hole in the ground.

Thanks to their field studies in southern Greece, where Cataglyphis ants are native, Fleischmann and her colleagues were able to prove that desert ants orient themselves to the Earth’s magnetic field during the learning walk phase. Pauline Fleischmann and Robin Grob were once again on site in Greece. This time, however, they not only investigated the ants’ orientation behavior while the magnetic field was being manipulated, but also looked for changes in the nervous system of Cataglyphis as an expression of the newly acquired experience.

A Faulty Magnetic Field Disrupts the Learning Process

The zoologists concentrated on young workers that had not yet undertaken any learning walks. The animals were only allowed to set off as part of the precisely planned experiments — sometimes under natural conditions, sometimes in a permanently manipulated magnetic field that, for example, displayed chaotic directions or did not allow horizontal orientation. With this faulty directional information, it was not suitable as a reliable reference system for the ants’ behavior to look back to the nest entrance during the learning walks.

The result: “Our neuroanatomical brain analyses show that ants exposed to an altered magnetic field have a smaller volume and fewer synaptic complexes in an area of the brain responsible for the integration of visual information and learning, the so-called mushroom body,” explain Fleischmann and Grob. In the central complex, the region of the ant’s brain in which spatial orientation is anchored, the same findings were observed under certain conditions.

The Number of Synaptic Connections Increases

Desert ants that were allowed to make their first excursions under natural conditions were clearly different. Their sensory experiences, a combination of information about the magnetic field, the position of the sun and the visual environment, triggered a learning process that was accompanied by structural changes in the neurons and an increase in synaptic connections in the aforementioned brain regions.

According to the scientists, this leads to the conclusion that magnetic information not only serves as a compass for navigation, but also as a global reference system that is crucial for the formation of spatial memory.

In Search of the Sensory Organ

The results of their experiments prove “that ants need a functioning magnetic compass during their learning walks in order to calibrate their visual compass and at the same time store images of the nest environment in their long-term memory,” as Pauline Fleischmann and Robin Grob say. At the same time, their research extends far beyond the field of compass calibration in ants. Wolfgang Rössler emphasizes that “the results provide valuable information on how multisensory stimuli can influence neuronal plasticity of brain circuits for navigation in a critical phase of brain maturation.”

In a next step, the team now wants to investigate in which sensory organ the desert ant receives the magnetic information and via which sensory pathways it is transmitted and processed. This has not yet been achieved with any animal species that orients itself to the Earth’s magnetic field. Due to their manageable and relatively small nervous system, insects, to which Cataglyphis belongs, offer a unique opportunity to investigate the neuronal basis of magnetic orientation at all levels.

The new research published in the Journal of Physiology conducted by an interdisciplinary consortium of clinicians and researchers led by University of Birmingham and collaborators in Germany.

The team found that male sex hormones, such as testosterone, also called androgenic anabolic steroids (AAS), which are misused for muscle building particularly among in young men can increase the risk of atrial fibrillation in individuals genetically predisposed to heart diseases.

Dr Laura Sommerfeld, Postdoctoral Researcher at the UKE Hamburg, who completed her PhD at the Institute of Cardiovascular Sciences at the University of Birmingham focusing on this work is lead author of the study.

Dr Sommerfeld said: “Our study can significantly contribute to understanding the impact on the heart health of young men who misuse anabolic steroids to increase muscle mass. Recent reports have shown that young men in particular are being targeted on social media such as TikTok being sold testosterone products, but we have shown how the misuse of steroids carries a specific risk that many people will not be aware of.”

Professor Larissa Fabritz, Chair of Inherited Cardiac Conditions at UKE Hamburg and Honorary Chair in the Institute of Cardiovascular Sciences at the University of Birmingham added:

“Heart muscle diseases like ARVC affect young, athletic individuals and can lead to life-threatening heart rhythm disturbances. Atrial fibrillation is a common condition in the general population. Elevated testosterone levels can result in an earlier onset of these diseases.”

The scientists examined potential effects on a condition called arrhythmogenic right ventricular cardiomyopathy (ARVC), which is genetically determined and primarily attributed to disruptions in the formation of cell connections critical for heart muscle stability.

The scientists initially confirmed, based on clinical patient data from UHB and elsewhere, that ARVC occurs more frequently and severely in men than in women. In laboratory experiments, they discovered that six weeks of AAS intake, combined with impaired cell connections, could lead to reduced sodium channel function in heart tissue and a slowing of signal conduction within the atria.

Dr Andrew Holmes, co-author and Assistant Professor in the Institute of Clinical Sciences at the University of Birmingham said:

“This work implies that young male individuals with key inherited genetic changes have a greater risk of developing electrical problems in the heart in response to anabolic steroid abuse.”