Systemic administration of the benzodiazepine receptor partial inverse agonist FG‐7142 disrupts corticolimbic network interactions

Stevenson, Carl W.; Halliday, David M.; Marsden, C.A.; Mason, Rob

doi:10.1002/syn.20414

Cited by 21 publications

(19 citation statements)

References 108 publications

(143 reference statements)

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“…This drug causes anxiety, impairs working memory and induces corticosterone release File, 1985, 1986;Murphy et al, 1996). FG-7142 also activates mPFC (Singewald et al, 2003;Stevenson et al, 2007Stevenson et al, , 2008 and dopamine transmission in this region (Murphy et al, 1996;Dazzi et al, 2001). Given that FG-7142 mimics various effects of stressors, our previous findings may also model an impairment of stress-induced mPFC function with MS.…”

mentioning

confidence: 60%

“…The five units which were putatively characterized as interneurons were omitted from the data analysis. A paucity of recordings from interneurons in mPFC has been observed in other studies (Homayoun et al, 2005;Laviolette et al, 2005;Stevenson et al, 2007Stevenson et al, , 2008 and is likely due to both anatomical and technical considerations. Anatomical studies indicate that the majority of neurons in mPFC are pyramidal cells (Gabbott et al, 1997).…”

Section: Discussionmentioning

confidence: 88%

“…As previously reported, systemic (i.v.) administration of FG-7142 had immediate and sustained effects on unit activity (Stevenson et al, 2007. Thus the mean (ϮS.E.M.)…”

Section: Discussionmentioning

confidence: 88%

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Early life programming of hemispheric lateralization and synchronization in the adult medial prefrontal cortex

et al. 2008

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Abstract-Neonatal maternal separation (MS) in the rat increases the vulnerability to stressors later in life. In contrast, brief handling (H) in early life confers resilience to stressors in adulthood. Early life programming of stress reactivity may involve the medial prefrontal cortex (mPFC), a region which modulates various stress responses. Moreover, hemispheric specialization in mPFC may mediate adaptive coping responses to stress. In the present study, neuronal activity was examined simultaneously in left and right mPFC in adult rats previously subjected to MS, H or animal facility rearing (AFR). In vivo electrophysiology, under isoflurane anesthesia, was used to conduct acute recordings of unit and local field potential (LFP) activity in response to systemic administration of N-methyl-␤-carboline-3-carboxamide (FG-7142), a benzodiazepine receptor partial inverse agonist which mimics various stress responses. MS decreased basal unit activity selectively in right mPFC. Basal LFP activity was reduced with MS in left and right mPFC, compared to AFR and H, respectively. Hemispheric synchronization of basal LFP activity was also attenuated by MS at lower frequencies. FG-7142 elicited lateralized effects on mPFC activity with different early rearing conditions. Activity in left mPFC was greater with AFR and MS (AFR>MS), whereas activity was predominantly greater with H in right mPFC. Finally, compared to AFR, MS reduced and H enhanced hemispheric synchronization of LFP activity with FG-7142 treatment in a dose-dependent manner.These results indicate that functionally-relevant alterations in mPFC GABA transmission are programmed by the early rearing environment in a hemisphere-dependent manner. These findings may model the hemispheric specialization of mPFC function thought to mediate adaptive coping responses to stressors. They also suggest the possibility that early environmental programming of hemispheric functional coupling in mPFC is involved in conferring vulnerability or resilience to stressors later in life.

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confidence: 60%

Section: Discussionmentioning

confidence: 88%

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Early life programming of hemispheric lateralization and synchronization in the adult medial prefrontal cortex

et al. 2008

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“…Automatic sorting (T-Dist E-M) methods were then used to separate the waveforms into individual units. The resulting clusters were inspected and the units were considered to be separate only if the cluster borders did not overlap (see Stevenson et al, 2007). Sorted spike trains were then analyzed with NeuroEXplorer v3.2 (NeuroExplorer, Littleton, Massachusetts).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of endocannabinoid metabolism attenuates enhanced hippocampal neuronal activity induced by kainic acid

Coomber

O’Donoghue

Mason

2008

Synapse

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The endogenous cannabinoid system regulates neuronal excitability. The effects of inhibiting fatty acid amide hydrolase (FAAH), the enzyme responsible for metabolism of the endocannabinoid anandamide, on kainic acid (KA)-induced neuronal activity were investigated in the rat in vivo, using the selective FAAH inhibitor URB597. Hippocampal neuronal ensemble unit activity was recorded in isoflurane-anesthetized rats using 16-wire microelectrode arrays. Separate groups of rats were administered with single doses of KA alone, KA and URB597 (0.3 or 1 mg kg 21 , i.p.), or URB597 (1 mg kg 21 ) alone. The role of the cannabinoid CB1 receptor in mediating the effects of URB597 was explored using the CB1 selective antagonists AM251, either alone or prior to KA and URB597 (1 mg kg 21 ) administration, and SR141716A, administered prior to KA and URB597 (1 mg kg 21 ). Neuronal firing and burst firing rates were examined in animals with confirmed dorsal hippocampal placements. KA induced an increase in both firing and burst firing rates, effects which were attenuated by URB597 in a dose-related manner. Pretreatment with AM251 or SR141716A partly attenuated the URB597-mediated effects on firing and burst firing rate. Rats treated with AM251 or URB597 alone did not exhibit any significant change in either firing or burst firing rates compared with basal activity. These results suggest that the inhibition of endocannabinoid metabolism can suppress hyperexcitability in the rat hippocampus, partly via a CB1 receptormediated mechanism. Synapse 62: 746-755, 2008. V

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“…Automatic sorting (T-Dist E-M) methods were then used to separate the waveforms into individual units. The resulting clusters were inspected and the units were considered to be separate only if the cluster borders did not overlap (see Stevenson et al 2007). (Paxinos and Watson 1998) for each experiment included in this study (n = 4 rats).…”

Section: Spike Sortingmentioning

confidence: 99%

Assessing cortico-hippocampal functional connectivity under anesthesia and kainic acid using generalized partial directed coherence

et al. 2010

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A significant challenge in modern neuroscience lies in determining the functional connectivity between discrete populations of neurones and brain regions. In this study, a variation of partial directed coherence, the generalized partial directed coherence (gPDC), along with a newly proposed critical value for gPDC, were applied on recorded local field potentials (LFPs) and single-unit activity, in order to assess information flow between medial prefrontal cortex (mPFC) and hippocampus and within the hippocampus of the rat brain, under isoflurane anesthesia and kainic acid-induced enhanced neuronal activity. Our findings suggest that, under anesthesia, there exists a continuous information flow from hippocampus towards mPFC, reversed mostly during activity bursts occurring in the mPFC. Moreover, there was a clear directional connection from the lateral towards medial dorsal hippocampus, most prominent in the beta frequency band (10-30 Hz). Kainic acid resulted in partially disrupting the reciprocal cortico-hippocampal connectivity and reversing the intra-hippocampal one. The biological implications of these findings on the effects of anesthesia and kainic acid in brain connectivity, along with implementation issues of gPDC analysis on field potentials and spike trains, are extensively discussed.

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Systemic administration of the benzodiazepine receptor partial inverse agonist FG‐7142 disrupts corticolimbic network interactions

Cited by 21 publications

References 108 publications

Early life programming of hemispheric lateralization and synchronization in the adult medial prefrontal cortex

Early life programming of hemispheric lateralization and synchronization in the adult medial prefrontal cortex

Inhibition of endocannabinoid metabolism attenuates enhanced hippocampal neuronal activity induced by kainic acid

Assessing cortico-hippocampal functional connectivity under anesthesia and kainic acid using generalized partial directed coherence

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