The ventral hippocampal regulation of prepulse inhibition and its disruption by apomorphine in rats are not mediated via the fornix.

Prepulse inhibition (PPI) of startle is a measure of sensorimotor gating that is impaired in schizophrenia. We have reported that PPI is regulated by the ventral hippocampus (VH) and that the PPI disruptive effects of the dopamine agonist apomorphine are enhanced 4 weeks after excitotoxic lesions of the VH. The mechanisms responsible for the VH influence on PPI are not understood, but have been ascribed to interactions between the VH and nucleus accumbens. In the present study, we examined whether the VH influence on PPI and its dopaminergic regulation is dependent on the integrity of the VH-accumbens projection via the fornix. First, the PPI-disruptive effects of intra-VH NMDA infusion were assessed after sham or electrolytic transection of the fornix. Second, the PPI-disruptive effects of apomorphine were assessed 1 month after excitotoxic or electrolytic lesions of the VH, or after fornix transection. Intra-VH N-methyl-D-aspartate infusion significantly disrupted PPI; this effect was unaffected by fornix lesions. The PPI-disruptive effects of apomorphine were significantly enhanced by excitotoxic or electrolytic lesions of the VH, but not by fornix transection. The influence of the VH on PPI and its dopaminergic regulation does not appear to be mediated via the fornix. The enhanced sensitivity to the PPI-disruptive effects of apomorphine after VH lesions is not dependent on excitotoxin-induced changes in the VH or its downstream projections.

Regulation of sensorimotor gating in rats by hippocampal NMDA: anatomical localization.

Prepulse inhibition (PPI) of the startle reflex is a measure of sensorimotor gating that is reduced in humans with certain neuropsychiatric disorders, including schizophrenia, and in rats after manipulations of limbic cortico-striato-pallido-pontine circuitry. We have reported that PPI is reduced after specific manipulations of the hippocampal complex (HPC) in rats, but the mechanisms for these effects remain poorly understood. For example, dopaminergic substrates clearly regulate PPI, but the PPI-disruptive effects of intra-HPC carbachol or NMDA are not reversed by D2 receptor antagonists. This study examined the anatomical specificity within the hippocampal complex of the PPI-disruptive effects of NMDA infusion. Startle magnitude and PPI were assessed after acute bilateral infusion of NMDA (0, 0.4 or 0.8 microg) into the dorsal subiculum (DS), region CA1, the ventral subiculum (VS), the rostral entorhinal cortex (ECr) and the caudal entorhinal cortex (ECc). A dorsal-ventral gradient for NMDA effects was observed, with a dose-dependent disruption of PPI after NMDA infusion into the VS or EC, but not the DS, and with intermediate level effects observed after NMDA infusion into CA1. A second set of studies confirmed that the failure of NMDA effects in the DS did not reflect site-related differences in startle magnitude or baseline levels of PPI. These findings demonstrate the importance of the ventral, but not the dorsal HPC, in the glutamatergic regulation of PPI.

Sensitivity to the dopaminergic regulation of prepulse inhibition in rats: evidence for genetic, but not environmental determinants.

Prepulse inhibition (PPI), a measure of sensorimotor gating, is reduced in schizophrenia patients and in rats treated with dopamine (DA) agonists. Reported strain and supplier-based differences in sensitivity to PPI-disruptive effects of DA agonists presumably reflect the differential impact of genetics and/or environment on DAergic substrates regulating PPI. In 2000, Harlan Laboratories established a Texas Sprague-Dawley line (SDHt; facility 211) using breeders from Indianapolis (SDHi; facility 202A). SDHi rats had been used, approximately 11 years earlier, to establish a colony in San Diego (SDHsd; facility 235). SDHt and SDHi rats are thus genetically similar, but raised in distinct environments; approximately 11 years of genetic "drift" separates SDHsd rats from both SDHi and SDHt rats. Harlan Long-Evans hooded rats (LEH; Madison, WI; facility 207) are genetically distinct from albino SDH. All except SDHsd rats were shipped to our facility by air freight. We used SDHt, SDHi, SDHsd, and LEH rats to assess genetic and environmental contributions to the DAergic regulation of PPI. Acoustic startle/PPI were assessed in rats treated with the D1/D2 agonist apomorphine (APO), the D2 agonist quinpirole, or the D1 agonist SKF 82958. The relative sensitivities to the PPI-disruptive effects were: APO: SDHt=SDHsd=SDHi>>LEH; SKF 82958: SDHt=SDHsd=SDHi (LEH not sensitive); quinpirole: SDHt=SDHsd=SDHi; SDHi>LEH. Strain/supplier differences in sensitivity to drug effects on startle magnitude did not correspond to patterns of PPI sensitivity. In these rats, strain differences in the DAergic regulation of PPI are most easily explained by genetic, rather than environmental influences that differentially impact both D1 and D2 substrates. This finding is consistent with published reports in other strains. Pharmacogenetic studies of PPI in rats may identify a genetic basis for a model of deficient sensorimotor gating in schizophrenia.

Evaluation of test media for routine monitoring of Escherichia coli in nonpotable waters.

Six test media, m-TEC, m-TEC with 4-methylumbelliferyl-beta-D-glucuronide (MUG), lauryl tryptose agar (LTA) with MUG, LTA with 5-bromo-4-chloro-3-indolyl-beta-D-glucuronide (X-Glue), EC medium with MUG, and lauryl tryptose broth with MUG, were evaluated for their usefulness in enumerating Escherichia coli in nonpotable waters on a routine basis. The media were chosen for their case of interpretation of target colonies, ability to allow enumeration at low and high concentrations, and ability to inhibit nontarget microorganisms. The recoveries on the test media were compared with those on three reference media, R2A, m-FC, and m-Endo, by analysis of spiked samples of filter-sterilized waters. The test media were then further tested for their ability to differentiate nontarget but closely related microorganisms. Statistical analysis indicated that the best recoveries were obtained with lauryl tryptose agar with added MUG and X-Gluc. The media were then tested with surface waters that could be expected to have high levels of total and fecal coliforms along with Escherichia coli.