| The prefrontal cortex(PFC), also known as frontal cortex, including the whole frontal cortex prior to the primary motor cortex area and supplementary motor areas, is defined as the premier association cortex. PFC appears at latest from systemic embryology and matures at latest from individual developmental biology, and is the only neocortex which is interconnected to the mediodorsal thalamic nucleus reciprocally. Based on morphological characteristics, the rat PFC consists of three subdivisions: dorsolateral prefrontal cortex(DLPFC), orbitofrontal cortex(OFC) and medial prefrontal cortex(MPFC). The MPFC is divided into dorsal region taking a small proportion of the MPFC, homologous to the DLPFC in primates and mainly involved in various behavioral modulations(e.g. eye movement), and ventral region taking a large proportion, connected densely with limbic system and mainly involved in modulations on emotion, cognition and visceral activities. The ventral region is structurally and functionally diverse, and comprises prelimbic cortex(PL) and infralimbic cortex(IL). PL has been implicated in various cognitive(e.g. attention regulation, working memory), emotion, executive functions, and so on, and thus is also considered as ‘cognitive-emotional cortex’. IL exerts a pronounced influence on visceral/autonomic nerve activities through its direct projections to the medulla gastrointestinal motor central(e.g. nucleus of the solitary tract, the dorsal motor nucleus of the vagus, nucleus ambiguus), and is consequently involved in regulating gastrointestinal and cardiovascular activities, and thus is also considered as ‘visceral motor cortex’. Both PL and IL not only have similar cytoarchitectonics, but also are densely interconnected reciprocally.Restraint water-immersion stress(RWIS) is well known as a common model applied in physiological, medical and psychological experiments. RWIS is a kind of high-duty compound stress, including physiological stress(e.g. hunger, restraint, cold water) and psychological stress(e.g. anger, conditioned fear, anxiety), and can cause seriously gastrointestinal dysfunction and even gastric ulcer. Our previous studies have confirmed that a hyperfunction of parasympathetic nervous system contributes to the peripheral mechanism of gastrointestinal dysfunction induced by RWIS. Concerning the central mechanism, it has been known that the primary nervous center–medulla gastrointestinal center and the higher-level center–hypothalamus are involved in the physiological process, but little to know about roles of the highest-level center–cerebral cortex in this process. Our previous studies explored the effects of RWIS on neuronal activities of the forebrain by c-Fos expression when rats were exposed to RWIS for 30, 60, 120, or 180 min. The most intense c-Fos induction was observed in the medulla gastrointestinal central and hypothalamus, and medial prefrontal cortex. The data strongly suggest that PL and IL are involved in the organismal response to RWIS. However, are both PL and IL involved in the process of modulating gastrointestinal function under the RWIS state, and what possible roles do both areas play, respectively? Does either PL or IL exert differential modulations on gastrointestinal function under the non-RWIS state and the RWIS state, and what are the possible mechanisms? What’s the functional relationship between PL and IL in the process of modulating gastrointestinal function? Until now, little is known about all of these questions. The purpose of the study was to investigate the modulation effects of MPFC on gastric function under both RWIS and non-RWIS states and its underlying mechanisms, and also the functional relationship between PL and IL in this modulation process.The present study consists of five experiments:Experiment 1: Dopamine(DA) is an important neurotransmitter and could combine diverse receptors of dopamine in both PL and IL to participate in emotional, cognitive and autonomic process. It’s well known that L-Glu is an excitatory neurotransmitter and its receptors are distributed widely in MPFC. In this experiment, we microinjected DA or L-Glu into PL or IL, respectively, and investigated its effects on gastric motility and gastric acid secretion. The results are as followed: 1) Following microinjection of DA(0.2 mol/L, 200 n L) into the middle and caudal regions of PL, the frequency of gastric motility was inhibited and the mean duration of contraction wave was temporarily extended significantly(P<0.05), and no other effects were detected regarding gastric acid secretion and other indices of gastric motility. 2) Microinjection of DA into the rostral, middle and caudal regions of IL had no significant effects on gastric motility or gastric acid secretion(P>0.05). 3) Microinjection of L-Glu into PL or IL had little effect on gastric function(gastric motility and acid secretion), respiratory frequency and heart rate. Conclusion: 1) neurons originated from the middle and caudal region of PL are modulated by DA and exert certain inhibitory effect on gastric motility in anesthetized rats, but no response on gastric acid secretion. In addition, in anesthetized rats, DA-sensitive neurons of IL do not modulate gastric function. 2) There were no functional connections between neurons excited by L-Glu in PL and IL and gastric functions in anesthetized rats.Experiment 2: RWIS can cause significant gastrointestinal dysfunction and increase the c-Fos induction in PL and IL, indicating their involvement in the organismal response to RWIS. What are the possible roles of PL and IL in gastric ulcer induced by RWIS? In this part, we compared the possibly differential effects of shammed or unilateral or bilateral MPFC lesions on gastric mucosa injury induced by RWIS via measuring gastric ulcer index in awake rats. The results are as followed: 1) When comparing with the sham-control group, the degree of gastric mucosa injury was decreased significantly in unilateral-lesion group and bilateral-lesion group(P<0.01); 2) The effect in bilateral-lesion group was prior to that in unilateral-lesion group(P<0.05). Conclusion: MPFC could regulate gastric function under the RWIS state.Experiment 3: Based on the results from Experiment 1 and Experiment 2, the aim of this experiment was to explore the roles of PL or/and IL in modulating gastric function(gastric motility and acid secretion) in awake non-RWIS and RWIS rats. The animals were divided into four groups: sham-control group(Group A), PL-bilateral-lesion group(Group B), IL-bilateral-lesion group(Group C), PL and IL-bilateral-lesion group(Group D). Gastric motility(especially the amplitude, motility index and percentage of contraction) and gastric acid secretion were compared among these four groups under awake non-RWIS and RWIS states, respectively. The results are as followed: 1) Under awake non-RWIS state, the average amplitude, motility index and percentage of contraction of lesion groups were increased significantly when compared with sham-control group(P<0.05). The degree of increase is: Group D>Group C>Group B.2) Following 4-h RWIS, gastric motility of Group A was increased significantly(P<0.05 or P<0.05). However, the average amplitude and motility index of Group B had no any changes during RWIS, and the average amplitude, motility index and percentage of contraction of Group C and Group D were decreased significantly(P<0.05 or P<0.05). The results suggest that lesions of PL and IL inhibited the gastric hyperfunction induced by RWIS. The degree of inhibition is: Group D>Group C>Group B. 3) In addition, compared with sham-control group, the volume of gastric juice and H+ quantity were increased significantly(P<0.05), and the HCO3- quantity was decreased significantly(P < 0.05). Conclusion: 1) Together with Experiment 2, in awake non-RWIS rats, MPFC plays an inhibitory role on gastric motility. The inhibitory effect on gastric motility of IL is more than that of PL, and cooperation of PL and IL has the higher effect on gastric motility than either PL or IL alone; 2) In RWIS rats, MPFC plays an important role on gastric motility and acid secretion. The enhancing effect of IL is more than that of PL, and cooperation of PL and IL has the higher effect on gastric function than either PL or IL alone.Experiment 4: To further explore what roles of different types of neurons of PL and IL in rats play under awake RWIS states, and relationship among neuronal activities between PL and IL. OmniPlex in vivo multi-channel neural signal recording system was used to investigate activities of single-unit discharges(Spikes) of pyramidal neurons and interneurons, and also local field potentials(LFPs) in both PL and IL in awake non-RWIS and in RWIS rats, respectively. The results are as followed: 1) In awake non-RWIS rats, burst firing rate of pyramidal neurons in PL was higher than that of IL(P<0.05), and burst firing rate of interneurons in IL was higher than that of PL(P<0.05). The results suggest that, 2) Most of pyramidal neurons and all of the interneurons in PL were inhibited during 4-h RWIS. With the time prolonged during 4-h RWIS, firing rate, burst firing rate and percentage of spikes in burst were decreased significantly(P<0.05 or P<0.05). In addition, the low-frequency signals of LFPs in PL were increased and high-frequency signals of LFPs in PL were decreased significantly during RWIS(P<0.05 or P<0.05), which was supported by the data obtained from power spectral density analysis and joint time-frequency analysis. The results strongly suggest that excitation of PL is decreased due to RWIS in rats. 3) Only few of pyramidal neurons and all of interneurons in ILwere inhibited significantly during RWIS in rats(P<0.05 or P<0.05), and most of pyramidal neurons were excited significantly during RWIS(P<0.05 or P<0.05), however, this excitatory effect only lasted one to two hours. Meanwhile, opposite to changing pattern of the LFPs in PL, the low-frequency signals of LFPs of IL were decreased and high-frequency signals of LFPs were increased during RWIS significantly(P<0.05 or P<0.05), which was supported by the data obtained from power spectral density analysis and joint time-frequency analysis. The results strongly suggest that excitation of IL is increased due to RWIS in rats. Conclusion: 1) In awake non-RWIS rats, pyramidal neurons of PL have relatively high excitability and could lead to the excitation of PL. However, interneurons of IL have relatively high excitability and could lead to the inhibition of IL. 2) RWIS could activate descending parasympathetic nervous system and arouse gastrointestinal dysfunction by inhibiting pyramidal neurons of PL and exciting pyramidal neurons of IL. 3) Neurons in PL and IL always show opposite activity patterns under either awake non-RWIS or RWIS state.Experiment 5: Given important roles of MPFC in cognitive, emotional and executive functions, and involvement of MPFC in the organismal response to RWIS, this experiment aimed to investigate changes of cognition, emotion and anxiety of rats after damaging MPFC by using an open field test(OFT). The results showed that lesion of MPFC produced increased levels of anxiety and conditioned fear, increased sensitivity to environmental stimuli and timidity, and also decreased cognitive ability. Conclusion: MPFC plays an inhibitory role in emotional activities. |
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