Effects of optogenetic inhibition of a small fraction of parvalbumin-positive interneurons on the representation of sensory stimuli in mouse barrel cortex.

Inhibitory interneurons play central roles in the modulation of spontaneous network activity and in processing of neuronal information. In sensory neocortical areas, parvalbumin-positive (PV+) GABAergic interneurons control the representation and processing of peripheral sensory inputs. We studied the functional role of PV+ interneurons in the barrel cortex of anesthetized adult PVCre mice by combining extracellular multi-electrode recordings with optogenetic silencing of a small fraction of PV+ interneurons. In all cortical layers, optogenetic inhibition caused an increase in spontaneous network activity from theta to gamma frequencies. The spatio-temporal representation of sensory inputs was studied by stimulating one or two whiskers at different intervals and analyzing the resulting local field potential (LFP) and single unit (SU) response. Silencing PV+ interneurons caused an increase in LFP response to sensory stimulation and a decrease in temporal discrimination of consecutive whisker deflections. The combined effect of whisker deflection and optogenetic inhibition was highly similar to the linear sum of the individual effects of these two manipulations. SU recordings revealed that optogenetic silencing reduced stimulus detectability by increasing stimulus-evoked firing rate by a constant offset, suggesting that PV+ interneurons improve signal-to-noise ratio by reducing ongoing spiking activity, thereby sharpening the spatio-temporal representation of sensory stimuli.

Roles of glutamate and GABA of the Kölliker-Fuse nucleus in generating the cardiovascular chemoreflex.

The Kölliker-Fuse (KF) nucleus is a part of the parabrachial complex, located in the dorsolateral pons. It is involved in the chemoreflex-evoked cardiovascular and respiratory changes, but the role of GABA and glutamate in cardiovascular chemoreflex has not been shown yet. This study was performed to determine the role of GABA, glutamate, and their interaction in the KF, in cardiovascular chemoreflex in anesthetized rat. The antagonists were microinjected into the KF, and arterial pressure, heart rate, and single-unit responses were recorded simultaneously. The chemoreflex was evoked by i.v. injection of KCN, consisted of a short pressor followed by long bradycardia responses. Both responses were significantly attenuated by injection of a synaptic blocker (CoCl2) into the KF, confirming involvement of the KF in generating the reflex. Microinjection of AP5, an NMDA receptor antagonist, into the KF significantly attenuated the pressor and bradycardia responses, while blocking the AMPA receptors by CNQX had no significant effect. Blockade of GABAA receptors by bicuculline methiodide (BMI) potentiated both responses. Co-injection of BMI and CNQX potentiated the responses too. Co-injection of BMI and AP5 had no significant effect on the pressor response but significantly attenuated the bradycardia response. In conclusion, the KF plays a role in generating cardiovascular chemoreflex via its glutamate NMDA but not AMPA receptors. GABA inhibits both components of this reflex through GABAA receptors. There is an interaction between GABAA and NMDA receptors in regulating the bradycardia response of the reflex. Single-unit results were also presented which were correlated with and supported the homodynamic findings.

Comparison of the Quality of Sleep and Intensity of Headache between Migraine, Tension Headache, and Healthy Children.

OBJECTIVES: Headache and sleep problems are commonly reported in children, and both can adversely impact the child's life. We aimed to compare the sleep quality and intensity of headache between school-age children with migraine as well as tension headache and healthy children. MATERIALS & METHODS: In this cross-sectional study, 198 children 6-12 yr old in three groups were enrolled from Aug 2015 to Mar 2016. Migraine and tension headache groups from the Outpatient Clinic of Imam Khomeini of Hamadan, western Iran and healthy group from elementary schools were randomly selected (66 children in each group). Data were collected using demographic questionnaire, Child Sleep Habits Questionnaire (CSHQ), Numeric Scale of Pain Intensity and Wong-Baker Faces Pain Rating Scale. The data were analyzed using SPSS by descriptive statistic and multivariate ANOVA, one way ANOVA, Chi-square, Kruskal-Wallis and linear regression tests. RESULTS: Approximately, 45.5% of children with migraine and 37.9% of them with tension headache had experienced severe headache. Only a significant relationship was seen between mean scores of headache intensity and sleep quality in migraine group (P<0.05). There was a significant difference in mean scores of sleep quality among three groups (P<0.001). CONCLUSION: The children with migraine experienced more unsuitable sleep in duration of severe headache. Highlighting the co-morbidity between intensity of headache and sleep problem of children with migraine and tension headache is important to improve treatment strategies and to know the impact of headache on their normal life.

α2 Receptors in the lateral parabrachial nucleus generates the pressor response of the cardiovascular chemoreflex, effects of GABAA receptor.

The lateral parabrachial nucleus (LPBN) is a pontine area involved in cardiovascular chemoreflex. This study was performed to find the effects of reversible synaptic blockade of the LPBN on the chemoreflex responses, and to find the roles of GABAA receptor and α2-adenoreceptor (α2-AR) in chemoreflex. It also aimed to seek possible interaction between GABA and noradrenergic systems of the LPBN in urethane-anesthetized male rats. Cardiovascular chemoreflex was activated by intravenous injection of potassium cyanide (KCN, 80 µg/kg). The cardiovascular responses of chemoreflex were evaluated before (control), 5 and 15 min after microinjection of each drug (100 nl) into the LPBN. Microinjections of cobalt chloride (5 mM), a reversible synaptic blocker, into the LPBN greatly attenuated the chemoreflex pressor and bradycardic responses indicating that the LPBN plays a main role in chemoreflex. Local injection of yohimbine (10 nmol), an α2-AR antagonist, attenuated the pressor response with no effect on bradycardic response, suggesting that α2-adrenoreceptors are involved in producing the pressor response of the chemoreflex. Microinjection of bicuculline methiodide (BMI, 100 pmol), a GABAA antagonist, into the LPBN augmented the pressor response and attenuated the bradycardic response, indicating that GABA inhibits the sympathetic output to the heart and vasculature. Sequential injection of yohimbine and BMI had no significant effect on the pressor response but attenuated the bradycardia. In conclusion, the LPBN is essential for the chemoreflex responses. The pressor response of the chemoreflex, at least partly, is produced by α2- adenoreceptors. GABA in the LPBN inhibits the cardiovascular system. Finally, there is no interaction between GABAergic and adrenergic neurons of the LPBN in producing the cardiovascular chemoreflex.

Interaction of GABA and norepinephrine in the lateral division of the bed nucleus of the stria terminals in anesthetized rat, correlating single-unit and cardiovascular responses.

The bed nucleus of the stria terminalis (BST) consists of multiple anatomically distinct nuclei. The lateral division, which receives dense noradrenergic innervation, has been implicated in cardiovascular regulation and modulation of responses to stress. This study is performed to identify the cardiovascular and single-unit responses of the lateral BST to norepinephrine (NE), involved adrenoceptors, and possible interaction with GABAergic system of the BST in urethane-anesthetized rats. NE, adrenoreceptor antagonists, and GABAA antagonist were microinjected into the lateral division of BST, while arterial pressure (AP), heart rate (HR), and single-unit responses were simultaneously recorded. NE microinjected into the lateral division of BST produced depressor and bradycardic responses. The decrease in AP and HR to NE was blocked by prazosin, an α1-adrenoreceptor antagonist, but not by yohimbine, an α2 antagonist. Furthermore, injections of the GABAA receptor antagonist, bicuculline methiodide (BMI), into the lateral BST abolished the NE-induced depressor and bradycardic responses. We also observed single-unit responses consisting of excitatory and inhibitory responses correlated with cardiovascular function to the microinjection of NE. In conclusion, these data provide the first evidence that microinjection of NE in the lateral division of BST produces depressor and bradycardic responses in urethane-anesthetized rat. The depressor and bradycardiac response are mediated by local α1- but not α2-adrenoceptors. α1-AR activates the GABAergic system within the BST, which in turn produces depressor and bradycardic responses.

Mechanism of the cardiovascular effects of the GABAA receptors of the ventral tegmental area of the rat brain.

The ventral tegmental area (VTA) contains GABA terminals involved in the regulation of the cardiovascular system. Previously, we demonstrated that blocking GABAA but not GABAB receptors produced a pressor response accompanied by marked bradycardia. This study was performed to find the possible mechanisms involved in these responses by blocking ganglionic nicotinic receptors, peripheral muscarinic receptors or peripheral V1 vasopressin receptors. Experiments were performed on urethane anesthetized male Wistar rats. Drugs were microinjected unilaterally into the VTA (100 nl). The average changes in mean arterial pressure (MAP) and heart rate (HR) were compared between pre- and post-treatment using paired t-test. Injection of bicuculline methiodide (BMI), a GABAA antagonist, into the VTA caused a significant increase in MAP and a decrease in HR. Administration (i.v.) of the nicotinic receptor blocker, hexamethonium, enhanced the pressor response but abolished the bradycardic response to BMI, which ruled out involvement of the sympathetic nervous system. Blockade of the peripheral muscarinic receptors by homatropine (i.v.) abolished the bradycardic effect of BMI, but had no effect on the pressor response, indicating that bradycardia was produced by the parasympathetic outflow to the heart. Both the pressor and bradycardic responses to BMI were blocked by V1 receptor antagonist (i.v.), indicating that administration of BMI in the VTA disinhibited the release of vasopressin into the circulation. In conclusion, we demonstrated that GABAergic mechanism of the VTA exerts a tonic inhibition on vasopressin release through activation of GABAA receptors. The sympathetic system is not involved in the decrease of blood pressure by GABA of the VTA.