We cordially invite you to the Ph.D. Seminar, which will be held on June 15, 2023 at 11.30 in the Konorski room (2^nd floor). The program includes 4 presentations:

1. MSc Cagdas Topcu
2. MSc Marta Bejtka
3. MSc Dagmara Holm-Kaczmarek
4. MSc Aleksandra Mielnicka

Information regarding speakers together with abstracts can be found below. The seminar will be held in a hybrid mode.

Link to the meeting: https://zoom.us/j/93461216853?pwd=Vk5DaWlMcTlhMHZ6Q2VRNVc1U2xidz09

ABSTRACTS

1. MSc Cagdas Topcu

Laboratory of Neuroinformatics & Laboratory of Brain and Mind Electrophysiology at the Gdansk University of Technology

Proposed supervisor: Prof. Daniel Wójcik, PhD, DSc

Proposed auxiliary supervisor – Dr. Michal T. Kucewicz (Gdansk University of Technology).

Title:

Neural Dynamics and Anatomical Targets in Verbal Memory Encoding: Insights from Intracranial Recordings

Abstract:

To effectively treat memory and cognitive deficits, it is crucial to have an understanding of the anatomical sites and neural activities that should be targeted with specific therapies. Emerging technologies for local brain stimulation provide enticing therapeutic possibilities; however, their application must be precise, focusing on specific neural activities at distinct times and within critical brain regions that are essential for memory formation. The areas critical for successful encoding of verbal memory and underlying neural activities were determined directly in the human brain with intracranial electrophysiological recordings in epilepsy and deep brain stimulation (DBS) patients. In this study, we used two datasets. We recorded a broad range of spectral activities across the cortex of 135 epilepsy patients and 6 DBS patients as they memorized word lists for subsequent free recall. In our dataset of epilepsy patients, the spectral power analysis revealed significant differences in low theta frequency (3–5 Hz) activities within the left anterior prefrontal cortex between subsequently recalled and forgotten words. The subsequent memory effect was more pronounced in lower frequency bands and anterior cortical regions. Notably, the peak of this memory signal was observed in a distinct area at the junction between the Broca's area and the frontal pole. Importantly, the memory effect in this specific region exhibited a significantly higher magnitude compared to other anatomically distinct areas (Tukey–Kramer test, p<0.05). To explore the relationship between deep brain regions and the more superficial parts of the brain, we employed dynamic functional connectivity analysis to investigate the mechanisms underlying verbal memory across different encoding durations and brain structures. Our results suggest a focal hotspot of human verbal memory encoding located in the higher-order processing region of the prefrontal cortex, which presents a prospective target for modulating cognitive functions in the human patients. The memory effect provides an electrophysiological biomarker of low frequency neural activities, at distinct times of memory encoding, and in one hotspot location in the human brain. Our DBS recordings have

demonstrated that dynamic connectivity measures undergo changes during the encoding of

verbal memory. In order to develop individualized approaches, it is essential to consider both

network dynamics and the temporal aspects involved.

2. MSc Marta Bejtka

Laboratory of Neuroinformatics

Proposed supervisor: Prof. Daniel Wójcik, PhD, DSc

Title:

Kernel Electrical Source Imaging method for reconstruction of sources of brain activity

Abstract:

Epilepsy is the fourth most common neurological disorder in the world. In spite of efficiency and a steady development of pharmacological treatments, every third epileptic patient suffers from intractable seizures. In these patients surgical intervention may be the only solution to alleviate the problem. Before resection, neurosurgeons implant electrodes deep in the brain or on the cortex surface to identify the epileptogenic zone based on the measured potentials.

Since the actual brain activity can be represented by the distribution of current sources generating the potentials, current source density (CSD) analysis of data recorded within the patient brain may lead to more precise localization of  seizures’ origin and better surgical outcome than currently used approaches.

We developed the kernel Electrical Source Imaging (kESI) method which can localize multiple sources from recordings at arbitrary electrode positions thus is effectively applicable for a specific patient's case. The advantage of kESI over previous work (Potworowski 2012) is that it accounts for spatial variations of brain conductivity and specific brain anatomy. For that purpose the electric field in the brain is modeled with the Finite Element Method (FEM). In the talk I will introduce the kESI method and show the reconstruction of the brain activity based on cortical and depth recordings.

3. MSc Dagmara Holm-Kaczmarek

Laboratory of Laboratory of Molecular Basis of Cell Motility

Proposed supervisor:  Dr. Adriana Magalska, PhD, DSc

Title:

Characterization of the ATRX helicase in rat hippocampal neurons

Abstract:

The ATRX helicase genetic mutation is a known cause of α-thalassemia mental retardation X-linked (ATRX) syndrome, a condition characterized by various symptoms. This particular chromatin remodeler plays a crucial role in the deposition of H3.3 at repetitive DNA elements, contributing to the formation of heterochromatin. Our initial immunofluorescence studies of ATRX in hippocampal neurons revealed its localization in condensed DAPI-dense regions, indicating a primary association with heterochromatin. However, we also observed its colocalization with markers of euchromatin in certain regions, suggesting a unique dualistic character of ATRX as a chromatin remodeler. Furthermore, when we performed knockdown experiments of ATRX in rat hippocampal neuronal cultures, we observed alterations in chromatin condensation, characterized by an increase in the number and volume of heterochromatin foci. Additionally, reduced expression of ATRX led to abnormal dendritic tree morphology and disrupted patterns of histone modifications, specifically hypermethylation of H4K20me2/me3. Notably, apart from its role in nuclear chromatin, we made an intriguing discovery that ATRX bodies are present within the nucleolus. The quantity of these nucleolar subdomains exhibited changes under specific circumstances associated with transcriptional activity.
Collectively, these findings highlight the importance of ATRX as a significant contributor to chromatin remodeling, while also emphasizing the need for further investigation into its precise mechanisms and functions.

4. MSc Aleksandra Mielnicka

Laboratory of Neurobiology

Proposed supervisor  - Prof. Leszek Kaczmarek, PhD, DSc

Proposed auxiliary supervisor – Dr. Piotr Michaluk, PhD .

Title:

Vesicular gliotransmitter release is regulated by neuron to astrocyte interaction

Abstract:

The interplay between neuronal circuits and astrocytic processes was described over two decades ago by the term “tripartite synapse”. It assumes that neurotransmitters activate metabotropic G_q-associated protein receptors leading to increase in cytosolic Ca²⁺ concentrations in astrocytes which results in the release of gliotransmitters. Thus understanding the mechanism of gliotransmitters secretion is an important step in our attempt to understand the modulation of neuronal transmission.

To study exocytosis in astrocytes we use total internal reflection fluorescence microscopy (TIRFM) and Synaptobrevin-2 tagged with pH-dependent GFP probe. Our model are transfected astrocytes in dissociated rat hippocampal and cortical neuron/glia cultures, as well as pure astrocytic cultures.

Our results indicate that the rate of spontaneous exocytotic gliotransmission is lower in mix hippocampal and cortical neuron/glia cultures than in the pure astrocytic. Moreover, electrical stimulation of mix hippocampal culture increases the frequency of exocytosis and this effect is even higher in cortical culture. Blocking Ca²⁺ release from the endoplasmic reticulum (ER) using 2-APB and Ryanodine does not influence this process and activation of group I metabotropic glutamate receptors with DHPG does not increase the rate of exocytosis which indicate that Ca²⁺ released from ER does not regulate astrocytic exocytosis. However, removing Ca²⁺ from the extracellular solution decreases the frequency of fusion events proving importance of extracellular source of Ca²⁺ in gliotransmission. Furthermore, blocking neuronal activity with TTX does not influence spontaneous astrocytic exocytosis, however it blocks the increase caused by electrostimulation.

To conclude, our results indicate that there is a correspondence between presence of neurons, extracellular Ca²⁺ signal localization and the efficiency of gliotransmitter release in astrocytes.