Neuroplasticity and Metabolism Research Group
Research topics
Our current research focuses on determining activity-dependent gene expression in neurons, local synaptic plasticity, and the roles of microRNAs in neurons and adipose tissue. The ultimate goal of all genetic manipulations introduced in our studies is to reveal their impact on behavior and whole-body metabolism.
MicroRNAs in synaptic plasticity
The aim of this project is to determine the role of microRNAs in the synaptic plasticity of neurons involved in memory-trace formation. We are searching for microRNAs involved in the regulation of the PI3K–Akt–mTOR signaling pathway, such as miR-103/107. We recently demonstrated that the loss of all microRNAs enhances memory formation in mice (Konopka et al., 2010).
To investigate the PI3K–Akt–mTOR pathway, we use inducible, conditional knockouts of the Dicer and Pten genes. For long-term cognitive testing in mice, we have developed specialized protocols for the IntelliCage system (Kiryk et al., 2020).
The role of microRNAs in AgRP neurons in the development of obesity
We aim to identify hypothalamic cell subpopulations that are critical for the development of obesity following microRNA loss in the forebrain of transgenic mutants (Vinnikov et al., 2014).
The research focuses on understanding how microRNAs influence the activity of AgRP neurons (agouti-related peptide) in the hypothalamus, which play a key role in appetite regulation and energy balance. Loss of microRNAs in these neurons may lead to impaired metabolic homeostasis, excessive food intake, and weight gain.
We analyze changes in the expression of target genes and the signaling pathways involved in the development of the obesity phenotype. Using transgenic techniques and RNA sequencing, we aim to identify specific microRNAs that may serve as potential therapeutic targets in obesity treatment.
c-Fos expression in the arcuate nucleus during fasting
We have shown that c-Fos expression changes in the arcuate nucleus during fasting. A strong c-Fos signal is observed from 3 to 24 hours after food removal. c-Fos expression colocalizes with AgRP/NPY neurons in the medial part of the arcuate nucleus.
Furthermore, we are able to induce c-Fos expression using optogenetics in satiated mice. To investigate its role in feeding control, we are working on silencing c-Fos expression using LV vectors and CRISPR technology.
MicroRNAs in white and brown adipose tissue
We investigate the role of microRNAs in peripheral tissues involved in metabolism, such as adipose tissue. Our work focuses on microRNAs induced during caloric restriction and their effects on animals’ subsequent motivation to seek food. In addition, we explore the role of microRNAs in thermogenesis generated by brown adipose tissue.
Effects of different diets on the mouse microbiome
We test four diets: standard, Western Diet, High-Fat Diet, and ketogenic diet, and examine their effects on the composition of the mouse microbiome. We also monitor metabolic parameters and the ways in which the brain regulates caloric intake.
The laboratory’s long-term goal is to integrate cognitive and metabolic projects and to test mice fed various diets using advanced cognitive assays in IntelliCage.
Discovering new hormones
To investigate the coding potential of long non-coding RNAs (lncRNAs), in 2012 the group of Prof. John Mattick developed a pipeline integrating transcriptomic and proteomic data called Pinstripe (Gascoigne et al., 2012). To validate the presence of newly identified candidate hormones, in collaboration with the Biological and Chemical Research Centre of the University of Warsaw, we screened proteomic data from human cerebrospinal fluid against a database of 226 putative peptides/hormones. We identified one potential protein/hormone, which is now being intensively investigated in the context of hunger/satiety regulation.