ORCID Profile
0000-0002-9816-266X
Current Organisation
Nottingham Trent University - Clifton Campus
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Publisher: Elsevier BV
Date: 05-2001
Publisher: Wiley
Date: 04-1995
DOI: 10.1111/J.1460-9568.1995.TB00661.X
Abstract: Training chicks on a one-trial passive avoidance task results in transient up-regulation of the N-methyl-D-aspartate (NMDA) receptor in the left intermediate medial hyperstriatum ventrale (IMHV) of the forebrain 30 min post-training. Injection of the non-competitive NMDA receptor inhibitor, (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten 5,10-imine maleate (MK-801), around the time of training renders chicks amnesic for the task. Training also results in enhanced expression of the immediate early gene (IEG) c-fos in the IMHV. To determine the relationship between NMDA receptor up-regulation and IEG induction during memory formation we have examined the expression of Fos, Jun and their related proteins 2 h following training in the presence/absence of the putative amnestic agent MK-801. Western blotting of IMHV s les revealed two protein bands with immunoreactivity to the Fos antibody at 47 and 54 kDa. Using an antibody to Jun, two immunoreactive bands were revealed at 39 and 54 kDa. All bands were enhanced in the left IMHV following passive avoidance training. Post-training intraperitoneal injections of MK-801 (75 mM) produced amnesia in approximately 50% of the birds when tested 1 h after training. Injection of MK-801 significantly attenuated expression of these proteins in birds rendered amnesic, but not in those that recalled the task. We conclude that NMDA receptor activation precedes immediate early gene expression in the memory formation cascade.
Publisher: Elsevier BV
Date: 1999
Abstract: The antibiotic chlor henicol, an inhibitor of mitochondrial protein synthesis, was used to investigate the time-related changes in protein synthesis following passive avoidance training in the day-old chick (white leghorn-black Australorp). Retention of memory for this simple learning task is known to be prevented by an inhibitor of cytosolic protein synthesis, anisomycin, in a biphasic manner, with the first phase of sensitivity occurring up to 90 min post-training and the second phase between 4 and 5 h post-training (Freeman, Rose, & Scholey, 1995). Birds received bilateral intracranial injections of chlor henicol (10 microl/hemisphere of a 7.4 mM solution) at various times relative to training and were tested 24 h later. This report shows that at the second phase of anisomycin susceptibility there was a chlor henicol-sensitive period (5 h post-training) which had an onset time less than 1 h after injection. The effect of chlor henicol appears not to be due to the mitochondria being energetically compromised since intracranial injections of an uncoupler of mitochondrial oxidative phosphorylation, 2,4-dinitrophenol (0.1 mM), did not disrupt memory formation when injected 5 h after training, even though it did cause amnesia when injected at the earlier time point of 20 min post-training. These results are discussed in the context of what is already known about memory formation in the day-old chick.
Publisher: Wiley
Date: 06-06-2002
DOI: 10.1046/J.1471-4159.2002.00923.X
Abstract: Coexpression of PSD-95(c-Myc) with NR1-1a/NR2A NMDA receptors in human embryonic kidney (HEK) 293 cells resulted in a decrease in efficacy for the glycine stimulation of [3 H]MK801 binding similar to that previously described for l-glutamate. The inhibition constants (K (I) s) for the binding of l-glutamate and glycine to NR1-1a/NR2A determined by [3 H]CGP 39653 and [3 H]MDL 105 519 displacement assays, respectively, were not significantly different between NR1-1a/NR2A receptors coexpressed +/- PSD-95(c-Myc). The increased EC(50) for l-glutamate enhancement of [3 H]MK801 binding was also found for NR1-2a/NR2A and NR1-4b/NRA receptors thus the altered EC(50) is not dependent on the N1, C1 or C2 exon of the NR1 subunit. The NR1-4b but not the NR1-1a subunit was expressed efficiently at the cell surface in the absence of NR2 subunits. Total NR1-4b and NR1-4b/NR2A expression was enhanced by PSD-95(c-Myc) but whole cell enzyme-linked immunoadsorbent assays (ELISAs) showed that this increase was not due to increased expression at the cell surface. It is suggested that PSD-95(c-Myc) has a dual effect on NMDA receptors expressed in mammalian cells, a reduction in channel gating and an enhanced expression of NMDA receptor subunits containing C-terminal E(T/S)XV PSD-95 binding motifs.
Publisher: Elsevier BV
Date: 10-2000
DOI: 10.1016/S0091-3057(00)00373-7
Abstract: The specific mitochondrial benzodiazepine receptor (MBR) agonist, FGIN 1-27, and antagonist, PK 11195, were used to investigate whether this receptor was involved in passive avoidance memory formation in the day-old chick. PK 11195 at a concentration of 1-10 microM was found to be amnesic when injected directly into the lobus parolfactorius (LPO) 5 h after training (P<.01). Unilateral injections of PK 11195 further showed that memory was only disrupted with injections into the right hemisphere (P<.01). Since the MBR is considered to be involved in the production of a neurosteroid that modulates GABAergic transmission, we injected bicuculline and muscimol, specific inhibitor and agonist, respectively, of the GABA(A) receptor, to see if either disrupted memory formation. The results of bilateral injections into the LPO at 5 h post-training indicated that enhanced GABAergic transmission was involved in memory formation since the inhibitor, bicuculline, caused amnesia (P<.01) and unilateral injections also showed that this effect was confined to the right hemisphere (P<.05). Since memory for passive avoidance learning is thought to involve both cytosolic and mitochondrial protein synthesis at this 5-h time point [Freeman FM, Young IG. Chlor henicol-induced amnesia for passive avoidance training in the day-old chick. Neurobiol Learn Mem 1999 :80-93.], we studied the effect of unilateral injections of chlor henicol (CAP) and anisomycin (ANI) during this second wave of protein synthesis and found that CAP only disrupted memory when injected into the right LPO 5 h post-training (P<.05). This lateralization to the right hemisphere was also seen when ANI was injected 4 h post-training (P<.05) but at 5 h, only bilateral injections of ANI could disrupt memory (P<.05). The results suggest a role for mitochondria and the GABAergic system in the retention of passive avoidance learning in the day-old chick.
Publisher: Elsevier BV
Date: 05-1995
Abstract: The antibiotic anisomycin (ANI), a protein synthesis inhibitor, was used to investigate the time-related changes in protein synthesis following passive avoidance training in the day-old chick. Retention of memory for this simple learning task is known to be prevented by protein synthesis inhibitors within the first hour post-training. Here we report a second, later time window during which inhibition of protein synthesis results in amnesia following one-trial passive avoidance training. Birds were given bilateral intracranial injections of ANI (10 microliters/hemisphere of a 30 mM solution) at various times relative to training and tested 24 h later. Injections given between 0.5 h prior to 1.5 h post-training or 4-5 h post-training, but not at later or at intervening times, resulted in amnesia. These results are discussed in the context of earlier findings, using the inhibitor of glycoprotein synthesis 2-deoxygalactose, that memory formation shows two glycoprotein-synthesis-dependent periods of sensitivity (Scholey, Rose, Zamani, Bock, & Schachner, 1993). The time windows of susceptibility of ANI and 2-Dgal are consistent with a model in which there are two waves of neural activity following training during the second, commencing 4 h after training, proteins are synthesized and then glycosylated as part of the establishment of an enduring memory trace.
Publisher: Cold Spring Harbor Laboratory
Date: 07-2000
DOI: 10.1101/LM.7.4.213
Abstract: Cytochrophin-4 (cyt-4), a tetrapeptide with opioid-like activity, caused amnesia when injected into chick forebrain 5 hr after passive-avoidance training. Bilateral injections of cyt-4 directly into the lobus parolfactorius (LPO) resulted in the chicks being amnesic for the training task 24 hr later, whereas unilateral injections of cyt-4 were effective only when injected into the right LPO. Cyt-4-induced amnesia was reversed by the general opioid antagonist, naloxone, indicating that cyt-4 was acting via an opioid receptor. The μ- and δ-opioid receptors (but not κ-opioid or ORL 1 -receptors) have been shown to be involved in memory formation 5 hr after training (Freeman and Young 2000). Because an antagonist of the μ-opioid receptor inhibited memory, we attempted to reverse the effect of cyt-4 using μ-opioid receptor agonists. Met[enk] was unable to reverse the inhibition of memory formation by cyt-4 suggesting that the μ-opioid receptor is not involved in this effect. However endomorphin-2 (endo-2) reversed the effect of cyt-4. We further investigated the action of endo-2 using an irreversible antagonist of the μ-receptor, β-funaltrexamine (β-FAN), and found that endo-2 reversed β-FAN-induced amnesia indicating that endo-2 was not acting on the μ-opioid receptor in the chick. Because unilateral injections of β-FAN were not amnesic (bilateral injections were amnesic) this provided further evidence that the effect of cyt-4 was not mediated via the μ-opioid receptor. Coinjection of the δ-receptor agonist, (D-Pen 2 , L-Pen 5 )enkephalin (DPLPE), reversed the disruptive effect of cyt-4 on memory. However, memory modulation via the δ-opioid receptor was not lateralized to the right hemisphere suggesting that cyt-4 does not act via this receptor either. It was shown that an antagonist of the ε-opioid receptor inhibited memory at the 5 hr time point. We conclude that the ε-opioid receptor or an unidentified opioid receptor subtype could be involved in the action of cyt-4.
Publisher: Elsevier BV
Date: 05-2000
DOI: 10.1016/S0006-8993(00)02181-8
Abstract: Long-term memory formation for passive-avoidance learning in the day-old chick is known to have two distinct time windows of protein synthesis (F.M. Freeman, S.P.R. Rose, A.B. Scholey, 1995. Two time windows of anisomycin-induced amnesia for passive-avoidance training in the day-old chick. Neurobiol. Learn. Mem. 63, 291-295). The lobus parolfactorius (LPO) is thought to be an important site for the second wave of protein synthesis which occurs 4-5 h after training. Birds received bilateral intracranial injections of agonists and antagonists for the mu-, delta-, kappa-opioid receptors and the opioid receptor-like (ORL(1)) receptor directly into the LPO at 5 h post-training and were tested for recall 24 h later. Also, 100 microM beta-funaltrexamine (beta-FAN), a mu-opioid receptor antagonist, significantly impaired memory formation (P<0.01). The delta-opioid receptor was also involved in memory formation at this time-point since antagonism of this receptor by 1 mM ICI-174,864 caused amnesia (P<0.01) which was reversed by the agonist, DPLPE. The kappa-opioid receptor appeared not to be involved during the second phase of neuronal activity since neither stimulation by dynorphin nor inhibition by nor-BIN caused amnesia for the task. The ORL(1) receptor agonist orphanin FQ also had no effect suggesting that this receptor was not involved at this 5-h time-point. Cytosolic and mitochondrial protein synthesis has been shown to be important in passive-avoidance learning in the day-old chick. Both chlor henicol (CAP) and anisomycin (ANI), inhibitors of mitochondrial and cytosolic protein synthesis, respectively, caused disruption when injected 5 h post-training into the LPO (P<0.05). Endomorphin-2 (Endo-2), a mu-opioid receptor agonist, reversed both the ANI- and CAP-sensitivity. However, DPLPE, a delta-opioid receptor agonist, only reversed the effect due to CAP. Possible mechanisms for these effects are discussed.
Publisher: Society for Neuroscience
Date: 28-01-2004
DOI: 10.1523/JNEUROSCI.3676-03.2004
Abstract: Gap junctions are intercellular channels that allow the passage of ions and small molecules between cells. In the nervous system, gap junctions mediate electrical coupling between neurons. Despite sharing a common topology and similar physiology, two unrelated gap junction protein families exist in the animal kingdom. Vertebrate gap junctions are formed by members of the connexin family, whereas invertebrate gap junctions are composed of innexin proteins. Here we report the cloning of two innexins from the leech Hirudo medicinalis . These innexins show a differential expression in the leech CNS: Hm-inx1 is expressed by every neuron in the CNS but not in glia, whereas Hm-inx2 is expressed in glia but not neurons. Heterologous expression in the paired Xenopus oocyte system demonstrated that both innexins are able to form functional homotypic gap junctions. Hm-inx1 forms channels that are not strongly gated. In contrast, Hm-inx2 forms channels that are highly voltage-dependent these channels demonstrate properties resembling those of a double rectifier. In addition, Hm-inx1 and Hm-inx2 are able to cooperate to form heterotypic gap junctions in Xenopus oocytes. The behavior of these channels is primarily that predicted from the properties of the constituent hemichannels but also demonstrates evidence of an interaction between the two. This work represents the first demonstration of a functional gap junction protein from a Lophotrochozoan animal and supports the hypothesis that connexin-based communication is restricted to the deuterostome clade.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Fiona Freeman.