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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: 3-O-Methyl-d-glucose (methylglucose) is often used to study blood-brain barrier transport and the distribution spaces of hexoses in brain. A critical requirement of this application is that it not be chemically converted in the tissues. Recent reports of phosphorylation of methylglucose by yeast and heart hexokinase have raised questions about its metabolic stability in brain. Therefore, we have re-examined this question by studying the metabolism of methylglucose by yeast hexokinase and rat brain homogenates in vitro and rat brain, heart, and liver in vivo. Commercial preparations of yeast hexokinase did convert methylglucose to acidic products, but only when the enzyme was present in very large amounts. Methylglucose was not phosphorylated by brain homogenates under conditions that converted 97% of [U-14C]glucose to ionic derivatives. When [14C]methylglucose, labeled in either the methyl or glucose moiety, was administered to rats by an intravenous pulse or a programmed infusion that maintained the arterial concentration constant and total 14C was extracted from the tissues 60 min later, 97–100% of the 14C in brain, 〉99% of the 14C in plasma, and 〉90% of that in heart and liver were recovered as unmetabolized [14C]methylglucose. Small amounts of 14C in brain (1–3%), heart (3–6%), and liver (4–7%) were recovered in acidic products. Plasma glucose levels ranging from hypoglycemia to hyperglycemia had little influence on the degree of this conversion. The distribution spaces for methylglucose were found to be 0.52 in brain and heart and 0.75 in liver.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous experiments in the rat have demonstrated that field CA1 and the subiculum project to the prefrontal cortex and that this direct unilateral pathway is excitatory. In the present study, anatomical and electrophysiological approaches were used to determine the transmitter mediating the excitatory responses in prefrontal cortex neurons to low-frequency stimulation of the hippocampus. The method of selective retrograde d-[3H]aspartate labelling was used to identify putative glutamatergic and/or aspartatergic hippocampal afferent fibres to the prefrontal cortex. Unilateral microinjection of d-[3H]aspartate into the prelimbic area of the prefrontal cortex resulted in the retrograde labelling of a fraction of hippocampal neurons. Some labelled cell bodies were distributed in field CA1 and the subiculum but larger numbers of neurons were detected in the ventral and intermediary subiculum. In a second series of experiments, the excitatory transmission from the hippocampus to the prefrontal cortex was pharmacologically analysed to provide further evidence for the involvement of glutamate and/or aspartate in the pathway. All prefrontal cortex neurons responding to the stimulation of the hippocampus were activated by selective agonists of the glutamate receptor subtypes α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-d-aspartate (NMDA), and these effects were selectively antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (APV) respectively. Most of the excitatory responses of prefrontal cortex neurons to single and paired-pulse stimulation of the hippocampus were antagonized by CNQX. APV only affected the excitatory response in a few cells. These results suggest that the hippocampal input to the prefrontal cortex utilizes glutamate and/or aspartate as a transmitter. Even though prefrontal cortex neurons responding to the stimulation of the hippocampus appear to have both AMPA and NMDA receptors, low-frequency stimulation of the hippocampo-prefrontal cortex pathway activates cortical neurons mostly through AMPA receptors.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 10 (1998), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The purpose of the present study was to examine whether cAMP-dependent protein kinase (PKA) was implicated in the process of long-term potentiation (LTP) in the hippocampal afferent fibre system to the prefrontal cortex in vivo. Using a biochemical approach, we measured PKA activity at different times after induction of LTP. We show that there is an NMDA receptor-dependent increase in PKA activity in the prefrontal cortex, only at five minutes after LTP induction. These data demonstrate a role of PKA in the induction and not the expression of cortical LTP and suggest that if PKA is involved in the late phase of LTP, it does not appear to be a persistent activation.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This study was undertaken to identify the neurotransmitter of the projection from the thalamic mediodorsal nucleus (MD) to the prefrontal cortex (PFC) using both retrograde transport of D-[3H]aspartate and electrophysiological approaches in the rat. Unilateral microinjections of D-[3H]aspartate performed into the prelimbic area of the PFC resulted in dense labelling of numerous cells in the ipsilateral MD. Excitatory responses were observed in PFC neurons after electrical stimulation of the MD. However, since cortical neurons project to the MD, these excitatory responses could have resulted either from the activation of the MD-PFC pathway and/or from the activation of recurrent collaterals of antidromically driven cortico-thalamic fibres. The conduction time of each of these two reciprocal pathways was determined by antidromic activation. Short latency excitatory responses resulted from activation of the MD-PFC pathway. They were predominantly observed in PFC neurons located in layer III and evoked at low frequency stimulation (0.3–1 Hz). These excitatory responses disappeared or were replaced by longer latency responses when higher frequency stimulations (3–10 Hz) were used. MD-evoked responses were blocked by the iontophoretic application of the AMPA receptor antagonist CNQX into the PFC. These results indicate that the MD-PFC pathway utilizes glutamate and/or aspartate as the neurotransmitter and that its activation induces excitation in PFC neurons through AMPA receptors. Even though the local application of the NMDA receptor antagonist APV was ineffective, a contribution of these receptors in MD-PFC transmission cannot be excluded.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 11 (1999), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We studied excitatory field potentials in the medial prefrontal cortex (mPFC, prelimbic area) to electrostimulation of the ventral hippocampus (CA1/subicular region) in the anaesthetized rat. Nine hundred stimulus trains (5 pulses at 250 Hz) applied at 1 Hz to the ventral hippocampus significantly and persistently depressed the amplitude and maximal slope (∼ 55% for each index) of the prelimbic field potentials, but did not change the latency of the maximal slope or peak negativity. Twelve stimulus trains (50 pulses at 250 Hz) applied subsequently at 0.1 Hz restored the depression back to control level, and this reversible depression was maintained for at least 13 h. Cumulative depressive effects on the prelimbic field potential amplitude and maximal slope were observed upon addition of stimulus trains in the hippocampus. An important implication of the results is that the direct pathway from the hippocampus to the mPFC in the rat retains long-term depression (LTD) as a neuroplastic form in vivo. This form could cooperate with long-term potentiation (LTP) and such a bi-directional synaptic plasticity in the prefrontal cortex contributes to how cortical neural networks store information.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 7 (1995), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This study investigated the role of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptor in the induction of long-term potentiation (LTP) in the hippocampal-prefrontal cortex pathway in vivo. Field potentials evoked by electrical stimulation of the CA1/subicular region were recorded in the prelimbic area of the prefrontal cortex under continuous perfusion of artificial cerebrospinal fluid in anaesthetized rats. High-frequency stimulation of the CA1/subicular region induced LTP of the evoked response in the prelimbic area of the prefrontal cortex. LTP was completely blocked when the selective NMDA receptor antagonist d-(-)2-amino-5- phosphonopentanoic acid (d-AP5; 200 μM), was perfused during the tetanus. Perfusion of D-AP5 did not affect normal transmission or pre-established LTP. These results demonstrate that induction of LTP in the hippocampal-prefrontal cortex pathway is an NMDA receptor-dependent process.
    Type of Medium: Electronic Resource
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