Department of Physiology
Research at the Department of Physiology focuses on the effects of stress on the cerebral cortex and subcortical brain structures, such as hippocampus, hypothalamic paraventricular nucleus (PVN) and dorsal raphe nucleus. These brain areas are involved in the regulation of stress response, while chronic stress may adversely influence their function. It has been postulated that chronic stress exposure contributes to cognitive and psychiatric disorders and, possibly, neurodegenerative diseases, therefore studying the mechanisms associated with the effects of stress on brain function is one of the major issues in modern neurobiology.
Research using animal models, conducted in our laboratory, showed that repetitive exposure to stress increased an excitatory glutamatergic neurotransmission in the examined brain structures, except for the hippocampus. It has been also shown that these stress-induced alterations in synaptic plasticity are accompanied by changes in glucocorticoid (GR) and mineralocorticoid (MR) receptors as well as inducible nitric oxide synthase (iNOS) levels.
The 5-HT7 receptor, which has been identified recently, is a promising research target in neuropsychopharmacology because of its potential role in the etiology of psychiatric disorders. Our studies have shown that 5-HT7 receptor activation results in an increase in the excitability of hippocampal CA1 pyramidal neurons and chronic stress increases the 5-HT7 receptor reactivity. Moreover, administration of 5-HT7 receptor antagonists prevents stress-induced alterations in synaptic transmission and neuronal excitability in all examined brain structures. Similar effects were obtained following repeated administration of antidepressants.
The primary research method used in the Department of Physiology involve electrophysiological recordings from isolated rat and mouse brain specimens (sections). Other methods include the whole-cell patch-clamp recording technique, field-potential recordings in neuronal populations as well as in vitro electrophysiology of neurons and neuroglia. Moreover, the levels of prostaglandins, cytokines and stress-related hormones are measured using biochemical methods. Protein levels are measured using Western blot technique.
The most important recent discoveries
It has been shown that multiple (14 days) administration of 5-HT7 receptor antagonist SB 269970 (1.25 mg / kg) to rats abolished the impact of 5-HT7 receptor activation on CA1 and CA3 pyramidal neurons in rat hippocampal slices.
We have found that three-day immobility stress increased neurotransmission in the excitatory synapses located on parvocellular neurosecretory cells of the hypothalamic paraventricular nucleus (PVN). In contrast, GABAergic neurotransmission remained unchanged, while cell membranes excitability of the of the examined neurons was decreased.
Nitric Oxide Synthase Inhibitor Attenuates the Effects of Repeated Restraint Stress on Synaptic Transmission in the Paraventricular Nucleus of the Rat Hypothalamus.
Magdalena Kusek, Anna Tokarska, Marcin Siwiec, Anna Gadek-Michalska, Bernadeta Szewczyk, Grzegorz Hess, Krzysztof Tokarski
Frontiers in cellular neuroscience, 10.3389/fncel.2017.00127
Nucleus incertus Orexin2 receptors mediate alcohol seeking in rats.
Hanna E Kastman, Anna Blasiak, Leigh Walker, Marcin Siwiec, Elena V Krstew, Andrew L Gundlach, Andrew J Lawrence
Neuropharmacology, S0028-3908(16)30292-1 10.1016/j.neuropharm.2016.07.006
Excitatory orexinergic innervation of rat nucleus incertus - Implications for ascending arousal, motivation and feeding control.
Anna Blasiak, Marcin Siwiec, Agnieszka Grabowiecka, Tomasz Blasiak, Anna Czerw, Ewa Blasiak, Alan Kania, Zenon Rajfur, Marian H Lewandowski, Andrew L Gundlach
Neuropharmacology, 10.1016/j.neuropharm.2015.08.014 S0028-3908(15)30060-5
Repeated handling, restraint, or chronic crowding impair the hypothalamic-pituitary-adrenocortical response to acute restraint stress.
A Gadek-Michalska, J Bugajski
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society,
- fluorescent microscopy
- G-protein coupled receptors
- glutamatergic receptors
- immobilization stress
- immune system
- ion channels
- long-term depression
- long-term potentiation
- neural circuit
- neural networks
- nitric oxide
- NMDA receptor
- serotonin receptors
- synaptic plasticity