Hippocampal slice

LTP) in hippocampal slices (89,90). LTP is believed to be a critical step in memory acquisition, and agents that possess the abiUty to augment this process in vivo are expected to be of benefit in memory enhancement. However, this compound has only demonstrated this property in vitro. In addition, because (11) does not appear to affect other neurotransmitter systems, as do other nootropics, the potential of BMY 21502 as a memory-enhancing agent is questionable. 

Ikeuchi Y, Hirai H, Okada Y, et al Excitatory and inhibitory effects of toluene on neural activity in guinea pig hippocampal slices. Neurosci Lett 138 63—66, 1993... 

BertoUini C, Ragozzino D, Gross C et al (2006) FractaUdne/CX3CLl depresses central synaptic transmission in mouse hippocampal slices. Neuropharmacol 51 816-821... 

Barth A, Barth L, Newell DW. Combination therapy with mk-801 and alpha-phenyl-tert-butyl-nitrone enhances protection against ischemic neuronal damage in organotypic hippocampal slice cultures. Exp Neurol 1996 141 330-336. 

Nearly all mechanistic studies of LTP have been carried out in the CAl region of hippocampal slices, where Schaffer collateral/commissural fibres make monosynaptic contacts with the dendrites of CAl pyramidal cells. It is generally accepted that the... 

Thompson, SM and Gahwiler, BH (1992) Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice cultures. J. Neurophysiol. 67 1698-1701. 

It is equally well known that if a neuron dies, or is destroyed, then any other neuron, which had been innervated by it, gradually becomes supersensitive to the NT it released. In the case of degenerating pyramidal cells this would be glutamate, the excitatory NT. Not surprisingly, undercutting the cortex in animals to produce a deafferentation of some of its neurons not only renders them more likely to show epileptic-like discharges but neurons in hippocampal slices from kindled rats and human focal cortex show supersensitivity to the excitatory amino acids. Such supersensitivity could make some neurons so easily activated that they become epileptic . 

In addition to its relatively high affinity at postsynaptic 5-HT receptors, MDMA exhibited high affinity for 5-HT uptake sites and has been shown to increase the release of [ H]5-HT and block [ H]5-HT uptake in vitro. These data suggest that some of the actions of MDMA may be mediated at presynaptic binding sites. With respect to [ H]5-HT release, MDMA has been reported to increase the release of [ H]5-HT from brain synaptosomes (Nichols et al. 1982) and hippocampal slices (Johnson et al. 1986). With respect to uptake blockade, MDMA has been reported to competitively inhibit H-5-HT uptake in vitro (Shulgin 1986). Furthermore, the neurotoxic effects of in vivo administration of MDMA on serotonin terminals can be blocked by concomitant administration of the 5-HT uptake blocker citalo-pram (Battaglia et al. 1988b Schmidt and Taylor 1987). Additional evidence in support of the hypothesis that MDMA produces some of its... 

In order to circumvent the difficulties of maintaining known, constant dmg concentrations in the brain in vivo, the hippocampal slice preparation was adapted to study the acute anatomic effects of psychotropic dmgs. This method was implemented in conjunction with Drs. K. Stratton and... 

In order to test the cytotoxic potential of PCA alone, hippocampal slices from untreated control animals were incubated in buffer containing PCA, over a wide range of concentrations (typically 50 pM) for 2 to 3 hours. 

The ineubation of slices directly in the parent compound (PCA) did not induce 5-HT depletion, and the 5-HT innervation in these slices was indistinguishable from that in control animals. Moreover, incubation of slices from PCA-treated animals in PCA-containing buffer did not prevent the recovery of 5-HT immunoreactive axons. The absence of 5-HT depletion after immersion of hippocampal slices in PCA strongly supports the proposition that PCA and related drugs are not directly neurotoxic. Thus, in vivo systemic administration of the drug appears necessary for the formation of a neurotoxic compound, such as a metabolite of the drug or of 5-HT, which is released. 

Contrasting in vitro and in vivo effects of p-chloroamphetamine (PCA) on 5-HT axons Immunocytochemical studies in hippocampal slices. Abstr Soc Neurosci 14 210, 1988. 

Figure 9 Graph of inhibition of acetylcholine release in superfused hippocampal slices versus CB1 receptor occupancy estimated from inhibition of [131I]AM281 binding.

Collins DR, Pertwee RG, Davies SN. Prevention by the cannabinoid antagonist, SR141716A, of cannabinoid-mediated blockade of long-term potentiation in the rat hippocampal slice. Br J Pharmacol 1995 115 869-870. 

Gifford AN, Ashby CR. Electrically evoked acetylcholine release from hippocampal slices is inhibited by the cannabinoid receptor agonist, WIN 55212-2, and is potentiated by the cannabinoid antagonist, SR 141716A. J Pharmacol Exp Ther 1996 277 1431-1436. 

Ameri A. Effects of the Aconitum alkaloid songorine on synaptic transmission and paired-pulse facilitation of CA1 pyramidal cells in rat hippocampal slices. Br J Pharmacol 1998 125 461—468. 

Lloyd, H. G. Fredholm, B. B. (1995). Involvement of adenosine deaminase and adenosine kinase in regulating extracellular adenosine concentration in rat hippocampal slices. Neurochem. Int. 26 (4), 387-95. 

Pak, M. A., Haas, H. L., Decking, U. K. Schrader, J. (1994). Inhibition of adenosine kinase increases endogenous adenosine and depresses neuronal activity in hippocampal slices. Neuropharmacology 33 (9), 1049-53. 

Lendvai, B., Sershen, H., Lajtha, A. et al. Differential mechanisms involved in the effect of nicotinic agonists DMPP and lobeline to release [3H]5-HT from rat hippocampal slices. Neuropharmacology. 35 1769, 1996. 

SSR-504734 is a potent, selective, and reversible inhibitor (IC50 = 18 nM) that is competitive with glycine [47,51]. The inhibitor rapidly and reversibly blocked the uptake of [14C]glycine in mouse cortical homogenates, which was sustained for up to 7 h. Complete cessation of blockade and return to glycine basal levels occurred prior to 24 h, which is in stark contrast to NFPS (>24 h). SSR-504734 potentiated a nearly twofold increase of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) in rat hippocampal slices and produced an increase in contralateral rotations in mice when microinjected into the striatum. Microdialysis experiments indicated that the inhibitor induced a rapid and sustained increase in extracellular glycine levels in the PFC of freely moving rats [51]. The compound also demonstrated efficacy in a variety of psychosis models [51-53]. SSR-504734 was reportedly in clinical trials for schizophrenia but discontinued after Phase I (data not disclosed) [54]. 

FIGURE 1.9 NO production from die CA1 region of die hippocampal slice following addition of 5mM L-glutamate (a) and lOpM /V-methyl-D-aspartate (b). (Reprinted with permission from Elsevier Publishing [50].)... 

A variety of different types of tissue preparation are used to study neurosecretion and synaptic transmission. A classical preparation is the frog NMJ (discussed below). The brain slice has been used for many years for biochemical studies of CNS metabolism and is a useful preparation for electrophysiological studies of synaptic transmission in the CNS. Slices can be oriented to maintain the local neuronal circuitry and can be thin, 0.3 mm, to minimize anoxia. The transverse hippocampal slice is widely used as an electrophysiological preparation to study synaptic plasticity (see Ch. 53). Primary cultures of neurons from selected CNS areas and sympathetic ganglia are also frequently used. They permit excellent visual identification of individual neurons and control of the extracellular milieu, but the normal neuronal connections are disrupted. 

Both the M2 and M4 receptors are, as indicated above, coupled to Gj pathways and appear to mediate similar responses. The M2 receptor is widely expressed in the CNS but also present in heart and smooth muscle, while M4 is preferentially expressed in the CNS, especially in forebrain. Ablation of the M2 receptor leads to complete loss of muscarinic-agonist-stimulated bradycardia [55]. In the CNS, deletion of the M2 receptor abolishes oxotremorine induced akinesia and tremors [56]. Memory and learning tasks including passive avoidance and working memory are impaired in M2-receptor knockout mice, and there is decreased LTP in hippocampal slices [12],... 

Ectoenzymes are involved in the rapid metabolism of ATP and other nucleotides in the extracellular space [2]. ATP applied to rat brain hippocampal slices is mostly converted to adenosine in less than a second. Some of the enzymes involved in ATP, UTP and nucleoside metabolism are depicted in Figure 17-2B. Inhibitors of these... 

Cellular mechanisms underlying hyperexcitability have been analyzed by electrophysiological studies of hippocampal slices isolated from animals with epilepsy 632... 

Traynelis, S. F. and Dingledine, R. Potassium-induced spontaneous electrographic seizures in a rat hippocampal slice. /. Neurophysiol. 59 259-276,1988. 

Traub, R. D., Miles, R. and Wong, R. K. Model of the origin of rhythmic population oscillations in the hippocampal slice. Science 243 1319-1325,1989. 

Inactivation of the a-synuclein gene by homologous recombination results in mice that appear largely normal [3]. Analysis of mice lacking y-synuclein has similarly failed to reveal any gross abnormalities [4]. In hippocampal slices from mice without a-synuclein, the replenishment of docked vesicles by reserve pool vesicles was slower than in slices from control mice. It suggests a physiological role for a-synuclein in the mobilization of synaptic vesicles. 

Clarke, V. R. J. and Collingridge, G. L. (2002) Characterisation of the effects of ATPA, a GLUk5 receptor selective agonist, on excitatory synaptic transmission in area CA1 of rat hippocampal slices. Neuropharmacology 42, 889-902. 

Fisher, R. S., and Alger, B. E. (1984) Electrophysiological mechanisms of kainic acid-induced epileptiform activity in the rat hippocampal slice. J. Neurosci. 4(5), 1312-1323... 

---