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L J Reece

Publications and source records attributed to L J Reece.

8 recordsLinked to original sources
PubMed1998

Onset of optic nerve conduction and synaptic potentials in superior colliculus of fetal rats studied in vitro.

This article describes the onset of electrical excitability and synaptic transmission in the retinocollicular pathway of the fetal and early postnatal rat, utilizing a novel in vitro preparation. Although the optic nerve is visible in embryonic day (E) 14 brain, its stimulation produced no response in the superior colliculus (SC) until E16 when a low voltage simple negative wave was evoked. At E17 these potentials were blocked rapidly, completely, and reversibly when choline was substituted for sodium or with the addition of cobalt ions. In the course of establishing the block with either of the above agents the latency of response increased, indicating an action on axonal transmission. By E20 the collicular evoked potential showed a short followed by a longer latency wave. The latter was blocked by the glutamate antagonist kynurenic acid, with latency unaffected. Further examination of potentials with the addition of glutamatergic receptor subtype blockers aminophosphonopentanoic acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione/6,7-dinitroquinoxaline- 2,3-dione (CNQX/DNQX) showed a clear abolition of the elicited potentials by E20 and older. Thus, fetal rat optic nerve fibers are capable of conduction in response to electrical stimulation as soon as they reach the SC at E16. Both sodium and calcium are involved. GABA-mediated modulation of axonal conduction is evident by E18. Glutaminergic synaptic transmission is established by E20. The timetable of fetal onset of capability to conduct and support synaptic transmission in the retinocollicular pathway is earlier than had previously been reported in vivo in the rat in which the superior colliculus neurones are said not to be driven by the optic nerve until 6 days post natal. This has relevance to the possible role of impulse activity in development of the pathway.

Animals↗
PubMed1998

Long-term plasticity at excitatory synapses on aspinous interneurons in area CA1 lacks synaptic specificity.

The synaptic specificity of long-term potentiation (LTP) was examined at synapses formed on aspinous dendrites of interneurons whose somata were located in the pyramidal cell layer of hippocampal area CA1. Intracellular recordings from slices prepared from rats were used to monitor excitatory postsynaptic potentials (EPSPs) elicited by extracellular stimulation in stratum radiatum. Two synaptic inputs were evoked at 0.5 Hz by stimulating axons adjacent to stratum pyramidale and s. lacunosum-moleculare. After obtaining baseline recordings (>/=10 min), one of the EPSPs was conditioned. The protocol involved tetanic stimulation, sometimes combined with somatic depolarization. Low-frequency stimulation of the two pathways was then resumed and EPSPs were recorded for <30 min. We observed both homosynaptic and heterosynaptic changes in synaptic strength. LTP and long-term depression (LTD) were seen in both pathways and all possible combinations of changes in the two EPSPs were observed, including heterosynaptic LTP associated with either homosynaptic LTP or LTD. Intracellular 1,2-bis (2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (10 mM) abolished alterations in synaptic strength. When axons in s. radiatum synapse onto a spiny pyramidal cell, synaptic specificity of LTP is preserved. However the results obtained from aspinous interneurons show that synaptic specificity of LTP is lost. These results are consistent with the hypothesis that spines provide postsynaptic mechanism(s) for conferring specificity to LTP.

Action Potentials↗
PubMed1994

Zinc induces hyperexcitability in the hippocampus.

The effects of zinc on neuronal excitability in rodent hippocampal slices were examined. In a paired-pulse protocol, the second population spike increased appreciably in the presence of zinc, whereas the first spike and the size of both population excitatory post-synaptic potentials remained unaffected. Changes in the second population spike produced by zinc were most pronounced when the afferents were stimulated with paired-pulses separated by 8-40 ms. The magnitude of altered excitability increased with the concentration of zinc in the perfusate. A long exposure to zinc in physiological concentration caused an epileptiform discharge followed by a period of depression. The effects of zinc could be mimicked with 1-3 microM bicuculline. We conclude that the integrity of the hippocampal inhibitory system is particularly vulnerable to zinc.

Action Potentials↗
PubMed1991

Effects of cholinergic agonists on two non-pyramidal cell types in rat hippocampal slices.

In the hippocampus, pyramidal cells (PCs) are not the only cell type sensitive to cholinergic stimulation. Two non-pyramidal cell types from animals as young as 8 days demonstrated clear, direct responses to application of cholinergic agonists. These cholinergic actions are excitatory, mostly blocked by muscarinic antagonists, and persist under conditions which block synaptic transmission (TTX, low Ca2+/high Mg2+). Cholinergic agonists may affect different conductances in interneurons than in PCs, sometimes resulting in rapid depolarization. Demonstration of direct excitatory cholinergic effects on inhibitory interneurons supports the view that cholinergically-evoked hyperpolarizations in PCs are due to local circuit interactions.

Acetylcholine↗
PubMed1991

Construction of a synthetic gene for an R-plasmid-encoded dihydrofolate reductase and studies on the role of the N-terminus in the protein.

R67 dihydrofolate reductase (DHFR) is a novel protein that provides clinical resistance to the antibacterial drug trimethoprim. The crystal structure of a dimeric form of R67 DHFR indicates the first 16 amino acids are disordered [Matthews et al. (1986) Biochemistry 25, 4194-4204]. To investigate whether these amino acids are necessary for protein function, the first 16 N-terminal residues have been cleaved off by chymotrypsin. The truncated protein is fully active with kcat = 1.3 s-1, Km(NADPH) = 3.0 microM, and Km(dihydrofolate) = 5.8 microM. This result suggests the functional core of the protein resides in the beta-barrel structure defined by residues 27-78. To study this protein further, synthetic genes coding for full-length and truncated R67 DHFRs were constructed. Surprisingly, the gene coding for truncated R67 DHFR does not produce protein in vivo or confer trimethoprim resistance upon Escherichia coli. Therefore, the relative stabilities of native and truncated R67 DHFR were investigated by equilibrium unfolding studies. Unfolding of dimeric native R67 DHFR is protein concentration dependent and can be described by a two-state model involving native dimer and unfolded monomer. Using absorbance, fluorescence, and circular dichroism techniques, an average delta GH2O of 13.9 kcal mol-1 is found for native R67 DHFR. In contrast, an average delta GH2O of 11.3 kcal mol-1 is observed for truncated R67 DHFR. These results indicate native R67 DHFR is 2.6 kcal mol-1 more stable than truncated protein. This stability difference may be part of the reason why protein from the truncated gene is not found in vivo in E. coli.

Amino Acid Sequence↗
PubMed1991

Effects of cholinergic agonists on immature rat hippocampal neurons.

We have investigated the effects of acetylcholine (ACh) and the cholinergic agonist carbachol on several cell types in the developing rat hippocampus. Pyramidal cells were responsive to cholinergic applications on the first day examined (postnatal day 2), indicating that postsynaptic cholinoceptivity develops early, perhaps before functional cholinergic innervation is present. These drugs, which induce a membrane depolarization and a conductance decrease in mature pyramidal cells, had similar effects (both magnitude and pharmacology) on most immature neurons. However, a minority of cells in immature tissue exhibited decreased input resistance (Rin) during the cholinergic-induced depolarization. This response is likely a product of cholinergic action on local circuit neurons: non-pyramidal-type cells from animals as young as 8 days demonstrated excitatory responses to application of cholinergic agonists. The study revealed a number of other features of immature cells which may have functional significance. Lucifer yellow injections showed significant dye coupling among CA3 (but not CA1) pyramidal cells in immature tissue, suggesting close metabolic and/or electrotonic coupling between those cells during development. Mature CA3 cells showed less dye coupling, but increased anomalous rectification, and longer time constant. Developmental changes in intrinsic cell properties, coupled to alterations in local circuit interactions, may alter tissue responsiveness to neurotransmitters such as acetylcholine, even if the receptor-mediated drug action remains stable.

Acetylcholine↗
PubMed1991

Nicotine exerts differential effects on different CA1 hippocampal cell types.

The effects of (-) nicotine hydrogen tartrate (NHT) were examined on several cell types in the CA1 region of rat hippocampus. The results indicate that nicotine may have a preferential net inhibitory effect on basket cells and an excitatory effect on oriens/alveus interneurons. The resultant effects of nicotine on pyramidal cells may thus be a product of complex local circuit interactions.

Animals↗