Nobuya Murakami

Role of presynaptic 5-HT1A and 5-HT3 receptors in modulation of synaptic GABA transmission in dissociated rat basolateral amygdala neurons.

Serotonin (5-HT) is considered to play a significant role in anxiety-related behaviors in animals through actions on the amygdaloid complex. To evaluate this role from the point of neurotransmitter release regulation, nystatin-perforated patch recording was employed on mechanically dissociated basolateral amygdala neurons containing functional synaptic boutons. GABAAergic miniature inhibitory postsynaptic currents (mIPSCs) were pharmacologically separated. In subsets of neurons, 8-OH-DPAT (1 microM), a specific 5-HT1A agonist, continuously inhibited mIPSC frequency without effects on mIPSC amplitude. By comparison, mCPBG (1 microM), a specific 5-HT3 agonist, transiently facilitated mIPSC frequency without effects on mIPSC amplitude. Together these results suggest the presynaptic existence of both 5-HT receptor subtypes. In these neurons, application of 8-OH-DPAT and its subsequent removal still suppressed mCPBG-induced responses on mIPSCs. This suppression was not caused by a reduction of presynaptic 5-HT3 receptor affinities to mCPBG and was completely eliminated by pretreatment with N-ethylmaleimide, a pertussis toxin sensitive GTP-binding protein inhibitor. In the neurons exhibiting presynaptic modulation with mCPBG but not 8-OH-DPAT, such suppression by exposure to 8-OH-DPAT was not observed. In conclusion, activation of presynaptic 5-HT1A receptors inhibited mIPSC frequency and at the same time suppressed, via a G-protein-mediated mechanism, the transient facilitation of mIPSC frequency produced by activation of presynaptic 5-HT3 receptors.

Calcium channel subtypes on single GABAergic presynaptic terminal projecting to rat hippocampal neurons

High voltage-activated Ca(2+) channel subtypes triggering GABA release from nerve terminals (boutons) projecting to rat hippocampal CA1 pyramidal neurons were studied. Evoked GABAergic inhibitory postsynaptic currents (eIPSCs) were recorded in response to focal stimulation of single boutons in mechanically dissociated neurons and in response to stimulation of nerve bundle in slice preparations. Nilvadipine (3 micro M), an L-type Ca(2+) channel blocker, completely inhibited eIPSCs evoked by stimulation of single boutons, but had no effect on eIPSCs evoked by stimulation of nerve bundle at low frequencies. Nilvadipine (3 micro M) did, however, prevent the potentiation of eIPSC amplitude following high-frequency stimulation of nerve bundles in the slice preparation. omega-Conotoxin-GVIA (3 micro M), an N-type Ca(2+) channel blocker, and omega-agatoxin-IVA (0.3 micro M), a P/Q-type Ca(2+) channel blocker, completely inhibited single bouton evoked eIPSCs in 33.3 and 83.3% of recordings, respectively. In response to low-frequency nerve bundle stimulation in the slice preparation, omega-conotoxin-GVIA (3 micro M), omega-agatoxin-IVA (0.1 micro M) both partially reduced eIPSC amplitude, with the residual component being abolished by Cd(2+) (0.1 mM). From these results, the following hypotheses could be drawn. (1). The distribution of P/Q- and N-type channels at a single bouton is nonuniform. (2. When a focal stimulation is applied to a single bouton, L-type channels play a significant role in a generation of an action potential which subsequently activates P/Q- and N-type channels at GABA release sites. (3). Action potentials conducted through axons in the slice preparation are sufficient to depolarize the bouton membrane, even when L-type channels are suppressed.

GABAB receptor transduction mechanisms, and cross‐talk between protein kinases A and C, in GABAergic terminals synapsing onto neurons of the rat nucleus basalis of Meynert

The transduction mechanisms underlying presynaptic GABAB receptor‐mediated inhibition of transmitter release have been characterized for a variety of synapses in the central nervous system (CNS). These studies have suggested a range of transduction mechanisms, including a role for second messengers such as protein kinases A (PKA) and C (PKC). In the present study, we have examined the intracellular signalling pathways underlying baclofen‐induced inhibition of GABA release from terminals synapsing onto rat basalis of Meynert neurons using patch‐clamp recordings. Baclofen, a selective GABAB receptor agonist, reversibly decreased both evoked and spontaneous, miniature, GABAergic inhibitory postsynaptic currents (eIPSCs and mIPSCs, respectively). Such baclofen actions were completely abolished by CGP55845A, a selective GABAB receptor antagonist, and by staurosporine, a non‐selective PKA and PKC inhibitor. The mIPSC frequency was still decreased by baclofen even in the presence of 4 AP, a K+ channel blocker, and Cd2+, a voltage‐dependent calcium channel blocker. Pharmacological activation or inhibition of PKC activity affected basal GABA release and mildly affected the response to baclofen. Inhibition of the cAMP/PKA cascade also affected basal GABA release and, in a subset of neurons, occluded the effects of baclofen, suggesting that the GABAB receptor‐mediated inhibitory action on GABA release was mediated via decreases in PKA activity. In addition, PKA inhibition occluded the effects of PKC modulation on both basal GABA release and on the response to baclofen. Our results characterize the transduction pathway of baclofen at these nucleus basalis of Maynert (nBM) synapses and show, for the first time, some cross‐talk between the cAMP/PKA and PKC pathways in mammalian presynaptic nerve terminals.

Combining steady-state constructive interference and diffusion-weighted magnetic resonance imaging in the surgical treatment of epidermoid tumors.

Abstract We describe the usefulness of three-dimen-sional Fourier transformation-constructive interference in steady-state (CISS) imaging and diffusion-weighted imaging (DWI) in the pre- and postoperative magnetic resonance imaging evaluation of intracranial epidermoid tumors. Two surgically proven epidermoid tumors in the cerebellopontine (CP) angle were not identified in conventional T1- and T2-weighted images because of a signal intensity similar to that of cerebrospinal fluid (CSF). CISS images clearly demonstrated displacement of the cranial nerves and a shift caused by a lesion in the cistern, but the signal intensity of the tumor by CISS was not sufficiently different from that of CSF to demonstrate the tumor directly. Using DWI, the tumor in the cistern was shown clearly by its increased signal intensity. Together, CISS and DWI compensated for each others disadvantages, and this combination was useful in guiding surgical treatment of epidermoid tumors in the CP cistern.

Assessment of Contact Location in Subthalamic Stimulation for Parkinson’s Disease by Co-Registration of Computed Tomography Images

Aims: To study the validity of a co-registration method for postimplantation computed tomography (CT) images for localizing the location of an intracranial deep brain stimulator. Methods: Three-dimensional reconstruction images of postimplantation CTs were co-registered with preoperative CTs by stereotactic planning software and used to localize 18 leads in the subthalamic nuclei of 10 patients with Parkinson’s disease. Our conventional method using superimposition of sagittal postimplantation magnetic resonance (MR) images were employed as a comparison. Results: The co-registered CT images separately visualized four individual contacts; on the other hand, the MR superimposition method demonstrated the leads as a group of no MR signal areas. Although laterality of the distal contact did not differ between two methods, the distal contact was located more anteriorly and inferiorly by the MR superimposition method than by the CT co-registration method. Conclusion: The CT co-registration method is superior to MR in visualizing deep brain stimulation contacts and resolves problems of MR safety in patients treated with a neurostimulator.

Melanotic neuroectodermal tumour of infancy at the anterior fontanelle

Abstract We describe a 4-month-old girl presenting with a melanotic neuroectodermal tumour of infancy at the anterior fontanelle. According to the neuroimaging findings, this tumour was found to lie epidurally, adherent to the dura mater, with thickening of the adjacent frontal bone. The tumour was dense on CT, while MRI showed a major part of the tumour to be isointense with cerebral cortex on both T1- and T2-weighted images. The neuroimaging and clinical features are briefly discussed.

Spectral Analysis of Field Potential Recordings by Deep Brain Stimulation Electrode for Localization of Subthalamic Nucleus in Patients with Parkinson’s Disease

Aims: Spectral analysis of local field potential (LFP) recorded by deep brain stimulation (DBS) electrode around the subthalamic nucleus (STN) in patients with Parkinson’s disease was performed. Methods: The borders of the STN were determined by microelectrode recording. The most eligible trajectory for the sensorimotor area of the STN was used for LFP recording while advancing the DBS electrode. Results: The low-frequency LFP power (θ- to β-band) increased from a few millimeters above the dorsal border of the STN defined by microelectrode recording; however, the low-frequency power kept the same level beyond the ventral border of the STN. Only high β-power showed close correlation to the dorsal and ventral borders of the STN. Conclusions: A spectral power analysis of LFP recording by DBS electrode helps with the final confirmation of the dorsal and ventral borders of the STN of Parkinson’s disease in DBS implantation surgery.

Focal cortical dysplasia type IIa underlying epileptogenesis in patients with epilepsy associated with Sturge-Weber syndrome.

In patients with epilepsy associated with Sturge‐Weber syndrome (SWS), epileptogenesis has been suggested to be caused by chronic ischemia in cortical areas affected by leptomeningeal angiomatosis or by ischemia‐related cortical malformations. However, this has not been fully verified electrophysiologically. We herein present two cases of SWS with medically intractable epilepsy in which the epileptogenic area involved focal cortical dysplasia (FCD) type IIa near the region of leptomeningeal angiomatosis. In both cases, the ictal‐onset zones were identified by chronic subdural electrodes, and the presence of FCD type IIa was shown histopathologically. In SWS, especially in association with focal leptomeningeal angiomatosis, FCD may thus play a major role in epileptogenesis. FCD should therefore be demonstrated by the collective findings of perioperative neurophysiologic examination, anatomic and functional neuroimaging, and histopathologic examination.

Utility of 3-T FLAIR and 3D short tau inversion recovery MR imaging in the preoperative diagnosis of hippocampal sclerosis: Direct comparison with 1.5-T FLAIR MR imaging

Purpose:  To examine the utility of fluid‐attenuated inversion recovery (FLAIR) imaging and three‐dimensional short tau inversion recovery (3DSTIR) imaging using a 3‐Tesla (3‐T) magnetic resonance (MR) imager in the preoperative evaluation of hippocampal sclerosis (HS).

Subthalamic Nucleus Stimulation Does Not Cause Deterioration of Preexisting Hallucinations in Parkinson’s Disease Patients

Background: Among the neuropsychiatric symptoms in Parkinson’s disease (PD) patients, hallucination can result from the disease itself or medical treatment. Hallucination associated with subthalamic nucleus stimulation (STN-DBS) has been reported; however, it is still unclear whether PD patients with a history of hallucination are appropriate candidates for STN-DBS or not. Aims: We investigated the effect of STN-DBS on preexisting hallucination associated with advanced PD. Methods: Eighteen STN-DBS patients were investigated retrospectively. The severity of hallucination was assessed by the thought disorder score on the Unified Parkinson’s Disease Rating Scale (UPDRS, part 1-item 2) in the patients’ interviews; the score 6 months after the initiation of STN-DBS was compared with the highest score throughout the preoperative history and the score 2 weeks before surgery. Results: Hoehn-Yahr stage and motor score (UPDRS part 3) were significantly improved following STN-DBS. Six months after the initiation of STN-DBS, the severity of hallucination, assessed by thought disorder score, did not increase, but rather decreased compared with the preoperative level (p < 0.05 by McNemar’s test). The daily levodopa equivalent dose was increased in 2 patients without the development of hallucination. On the other hand, anti-parkinsonian drugs were totally withdrawn in 1 patient, but without improvement of hallucination. Conclusions: Our findings indicate that STN-DBS surgery does not always lead to deterioration of preexisting hallucination in PD. In advanced PD, hallucination involves a multifactorial pathogenesis and a history of hallucination is not a contraindication to STN-DBS surgery.