Impact of transient correction of increased adrenocortical activity in hypothalamo-damaged, hyperadipose female rats

Objective: To explore the effects of transient correction of enhanced corticoadrenal activity in monosodium L-glutamate (MSG)-damaged female rats on peripheral insulin sensitivity and in vitro retroperitoneal (RP) adipocyte function. Designs: A dose of 4 mg/g body weight (BW) of MSG or vehicle (CTR) was i.p. injected, once every 2 days, between days 2 and 10 of age, in female rats. Intact and 21 day-operated (sham or adrenal enucleation (AE)) rats from both (CTR and MSG) groups were used for experimentation on day 120 of age. Circulating levels of several hormones, in basal and after i.v. high-glucose load conditions, and RP adiposity morphology and function were then evaluated. Results: MSG rats developed increased adrenocortical function, hyperadiposity, hyperleptinemia, hyperinsulinemia and decreased peripheral insulin sensitivity. These characteristics were fully reversed after transient correction of corticoadrenal hyperactivity induced by AE. In addition, in vitro experimentation with isolated RP adipocytes indicated that cells from intact MSG animals displayed decreased sensitivity to insulin and dexamethasone stimulation of leptin secretion. Interestingly, adipocyte dysfunction in MSG rats was fully abrogated after AE-induced transient correction of insulinemia, leptinemia and adrenocortical activity. Importantly, the reversion of these metabolic abnormalities, induced by AE for 21 days, in MSG animals did occur, despite no significant changes in BW values. Conclusion: Our results support that the changes in adipocyte characteristics and peripheral insulin resistance, developed in this pseudo-obese female rat model, are mainly due to increased glucocorticoid production. Importantly, appropriate correction of the enhanced adrenocortical activity fully reversed these abnormal functions.Instituto Multidisciplinario de Biología CelularFacultad de Ciencias MédicasFacultad de Ciencias Exacta

Continuous representations of speed by striatal medium spiny neurons

The striatum is critical for controlling motor output. However, it remains unclear how striatal output neurons encode and facilitate movement. A prominent theory suggests that striatal units encode movements in bursts of activity near specific events, such as the start or end of actions. These bursts are theorized to gate or permit specific motor actions, thereby encoding and facilitating complex sequences of actions. An alternative theory has suggested that striatal neurons encode continuous changes in sensory or motor information with graded changes in firing rate. Supporting this theory, many striatal neurons exhibit such graded changes without bursting near specific actions. Here, we evaluated these two theories in the same recordings of mice (both male and female). We recorded single-unit and multiunit activity from the dorsomedial striatum of mice as they spontaneously explored an arena. We observed both types of encoding, although continuous encoding was more prevalent than bursting near movement initiation or termination. The majority of recorded units did not exhibit positive linear relationships with speed but instead exhibited nonlinear relationships that peaked at a range of locomotor speeds. Bulk calcium recordings of identified direct and indirect pathway neurons revealed similar speed tuning profiles, indicating that the heterogeneity in response profiles was not due to this genetic distinction. We conclude that continuous encoding of speed is a central component of movement encoding in the striatum

Effect of restrained versus free drying on hygro-expansion of hardwood and softwood fibers and paper handsheet

Earlier work on the hygro-expansion of paper states that the larger hygro-expansivity of freely compared to restrained dried handsheets is due to structural differences between the fibers inside the handsheet. To study this hypothesis, first, the hygro-expansion of freely and restrained dried, hardwood and softwood handsheets has been characterized. Subsequently, the transient full-field hygro-expansion (longitudinal, transverse, and shear strain) of fibers extracted from these handsheets was measured using global digital height correlation, from which the micro-fibril angle was deduced. The hygro-expansivity of each individual fiber was tested before and after a wetting period, during which the fiber’s moisture content is maximized, to analyze if a restrained dried fiber can “transform” into a freely dried fiber. It was found that the longitudinal hygro-expansion of the freely dried fibers is significantly larger than the restrained dried fibers, consistent with the sheet-scale differences. The difference in micro-fibril angle between the freely and restrained dried fibers is a possible explanation for this difference, but merely for the hardwood fibers, which are able to “transform” to freely dried fibers after being soaked in water. In contrast, this “transformation” does not happen in softwood fibers, even after full immersion in water for a day. Various mechanisms have been studied to explain the observations on freely and restrained dried hardwood and softwood, fiber and handsheets including analysis of the fibers’ lumen and cross-sectional shape. The presented results and discussion deepens the understanding of the differences between freely and restrained dried handsheets.</p

The Effects of Social Interactions on Learning and Memory in the Honey Bee Apis Mellifera

The honey bee Apis mellifera has been used to study the genetics of learning and memory for several decades. In Chapter 2, a literature review revealed that learning and memory phenotypes are highly heritable. Several quantitative trait loci and specific genes which code for neurotransmitter receptors were identified. Whereas transcriptomic approaches showed that the process of learning and memory involves hundreds of genes. Although understanding the genetic components is crucial, it is also important to understand how environmental factors affect learning and memory. In Chapter 3, I investigate the effect of social interactions on discrimination learning by randomly assigning bees into three different social groups: 1 bee, 8 bees, and 32 bees. Using the proboscis extension conditioned response test, I found that the fewer social interactions a bee experiences, the more responsive she is to sucrose. Bees raised in groups of 32 had the best performance in discrimination learning

Impact of transient correction of increased adrenocortical activity in hypothalamo-damaged, hyperadipose female rats

Objective: To explore the effects of transient correction of enhanced corticoadrenal activity in monosodium L-glutamate (MSG)-damaged female rats on peripheral insulin sensitivity and in vitro retroperitoneal (RP) adipocyte function. Designs: A dose of 4 mg/g body weight (BW) of MSG or vehicle (CTR) was i.p. injected, once every 2 days, between days 2 and 10 of age, in female rats. Intact and 21 day-operated (sham or adrenal enucleation (AE)) rats from both (CTR and MSG) groups were used for experimentation on day 120 of age. Circulating levels of several hormones, in basal and after i.v. high-glucose load conditions, and RP adiposity morphology and function were then evaluated. Results: MSG rats developed increased adrenocortical function, hyperadiposity, hyperleptinemia, hyperinsulinemia and decreased peripheral insulin sensitivity. These characteristics were fully reversed after transient correction of corticoadrenal hyperactivity induced by AE. In addition, in vitro experimentation with isolated RP adipocytes indicated that cells from intact MSG animals displayed decreased sensitivity to insulin and dexamethasone stimulation of leptin secretion. Interestingly, adipocyte dysfunction in MSG rats was fully abrogated after AE-induced transient correction of insulinemia, leptinemia and adrenocortical activity. Importantly, the reversion of these metabolic abnormalities, induced by AE for 21 days, in MSG animals did occur, despite no significant changes in BW values. Conclusion: Our results support that the changes in adipocyte characteristics and peripheral insulin resistance, developed in this pseudo-obese female rat model, are mainly due to increased glucocorticoid production. Importantly, appropriate correction of the enhanced adrenocortical activity fully reversed these abnormal functions.Instituto Multidisciplinario de Biología CelularFacultad de Ciencias MédicasFacultad de Ciencias Exacta

The Treatment od alcoholism regarding the court orders

Cilj: Istražiti postoje li razlike u trajanju apstinencije, prihvaćenosti liječenja alkoholizma te uključenosti u rad KLA između skupina ispitanika kojima je sudskim mjerama određeno liječenje alkoholizma od skupine ispitanika koji se liječe bez prisile. Ispitanici i metode: U ovoj presječnoj studiji sudjelovalo je 60 ispitanika podijeljenih u 2 skupine. Eksperimentalnu skupinu činilo je 30 ispitanika kod kojih je provedeno liječenje alkoholne ovisnosti u okviru izrečenih sudskih mjera tijekom 2013., 2014. i 2015. godine. Kontrolnu skupinu činilo je 30 ispitanika koji su se liječili od alkoholizma dobrovoljno. Svi su potpisali informirani pristanak za dobrovoljno sudjelovanje u istraživanju. Bilježeni su sociodemografski podaci, broj bodova na MAST ocjenskoj skali i Skali zadovoljstva životom, dok se kratkim intervjuom dobio broj bodova u sklopu GAF ocjenske skale. Rezultati: Vrijednosti MAST-a, broj ambulantnog/bolničkog liječenja te uključenost u KLA bili su značajno viši kod ispitanika koji se liječe bez prisile u odnosu na ispitanike koji se liječe u okviru sudske mjere. Skala zadovoljstva životom pokazala je nešto više vrijednosti ispitanika koji se liječe kroz sudsku mjeru, dok su prema GAF skali ocjene bez značajnih razlika u odnosu na skupine. Zaključak: Tendenciju duže apstinencije i bolje prihvaćenosti liječenja imali su ispitanici koji su se svojevoljno liječili iz čega proizlazi da je dobrovoljno liječenje bolje od liječenja pod sudskom mjerom, no uputno je napraviti daljna istraživanja.Objectives: The aim of this study was to investigate whether there are differences in the duration of alcohol abstinence, acceptance of the treatment of alcoholism and involvement in the Club of Treated Alcoholics between two groups – one consisted of participants who were treated due to the court order and the other, treated voluntarily. Participants and methods: In this cross-sectional study there were 60 participants divided into 2 groups. The experimental group consisted of 30 participants who had been previously treated for alcoholism due to court orders enunciated during 2013, 2014 and 2015. Control group consisted of 30 participants who had been previously treated for alcoholism voluntarily. All of the participants have signed the informed consent which stated that they are willing to participate in the study. Socio-demographic data were collected, as well as the score of MAST scale and The Satisfaction with Life Scale. A brief interview was conducted so the score of GAF scale could be collected. Results: Score of MAST scale, number of times of being treated in dispensary/hospital and involvement in the Club of Treated Alcoholics were significantly higher in the group of voluntarily treated participants in comparison to the group of court-order treated participants. The Satisfaction with Life Scale indicated slightly higher scores in the group of court-order treated participants, while the GAF scale did not indicate any significant difference between the groups. Conclusion: The tendency of a longer time of abstinence and better acceptance of the treatment was reported in the voluntary group. Therefore, the final conclusion is that the treatment of alcoholism has better results if the participants are involved in it voluntarily rather than if they are being court-ordered. However, more research should be done on this particular subject

Role of M4 muscarinic receptors in the central nervous system

Muskarinové receptory typu 4 jsou jedním z pěti podtypů muskarinových receptorů, které patří spolu s receptory nikotinového typu mezi tzv. cholinergní receptory. Po aktivaci receptoru vyvolané vazbou acetylcholinu dochází k přenosu signálu do buňky prostřednictvím G-proteinů umístěných na plazmatické membráně, kdy muskarinové receptory typu 4 jsou spřaženy s Gi/o proteiny. Receptory M4 se stejně jako ostatní podtypy muskarinových receptorů vyskytují v centrální i periferní nervové soustavě. V centrální nervové soustavě je jejich výskyt nejvýraznější v oblasti striata a hipokampu. M4 receptory mají celou řadu regulačních funkcí, z nichž nejvýznamnější je pravděpodobně jejich vliv na lokomoci skrze dopaminergní systém ve striatu. Muskarinové receptory typu 4 se účastní i celé řady behaviorálních a kognitivních dějů, díky čemuž jsou zkoumány jako potenciální cíl pro léčbu duševních onemocnění. Klíčová slova: muskarinové receptory, M4 muskarinové receptory, GPCRs, cholinergní systém, centrální nervová soustavaMuscarinic receptors type 4 are one of the five subtypes of muscarinic receptors, that are members of cholinergic receptors family, together with nicotinic receptors. An acetylcholine binding on the receptor triggers the receptor activation and the signal transmission into the cell by G-proteins located on plasmatic membrane, in the case of muscarinic receptors type 4 by Gi/o proteins. The M4 receptors are, just like other subtypes on muscarinic receptors, located in central and peripheral nervous system. In the central nervous system, they are mostly located in striatum and hippocampus. The M4 receptors have a whole range of regulative functions, the most significant one is most likely the regulation of a locomotion in striatum by the dopaminergic system. The muscarinic receptors type 4 are involved in many behavioural and cognitive processes and are therefore studied as potential drug target for the treatment of mental disorders. Key words: muscarinic receptors, M4 muscarinic receptors, GPCRs, cholinergic system, central nervous systemKatedra fyziologieDepartment of PhysiologyPřírodovědecká fakultaFaculty of Scienc

Redundant Neuromodulatory Mechanisms That Control Fear Memory Consolidation

The ability to reliably and powerfully store memories for frightening experiences is crucial to survival in an ever-changing and potentially dangerous environment. Consolidation is the process by which long-term memories are stored in the brain, and much is understood about the processes that occur within a neuron in the hours after a learning event that stabilize learning-induced changes. However, the specific mechanisms through which fear exacerbates those processes remains unclear. Neuromodulators are a prime object of research to understand the consolidation of fear memory given that their release is a hallmark of the fear response. While several neuromodulatory systems are known to facilitate consolidation, no individual system yet appears to be essential. This dissertation explores the hypothesis that several neuromodulators work together to ensure proper consolidation of fear memory. The research contained in this dissertation employs pharmacologic and genetic manipulation of individual neuromodulatory receptor systems and associated intracellular signaling pathways to determine the essential neurobiology for consolidating of Pavlovian fear conditioning in mice. The results of this investigation reveal that β2-adrenergic, D5-dopaminergic and M1-muscarinic receptors in the basolateral amygdala (BLA) are essential to fear conditioning in a redundant manner, wherein two or more receptor types must be blocked in order to prevent consolidation. Furthermore, these three receptors are observed to redundantly activate phospholipase C (PLC), which this dissertation shows is necessary for consolidation in the BLA. Finally, evidence is provided to suggest that PLC promotes fear memory consolidation by inhibiting a voltage-dependent potassium channel (KCNQ/M) that regulates neuronal excitability and also appears to control consolidation. Together, this dissertation proposes that fear-induced neuromodulatory release promotes consolidation through redundant neuromodulatory activation of PLC, which puts the BLA in an excitable state that does not persist into the consolidation window after emotionally neutral experiences

A biophysical model of striatal microcircuits suggests delta/theta - rhythmically interleaved gamma and beta oscillations mediate periodicity in motor control

First author draf