Changes in single unit activity in the lateral hypothalamic area of goats during feeding.

In order to clarify the location of feeding centers in the ruminant brain, this study used a single-unit activity (SUA) recording electrode to investigate the existence of appetite-regulating neurons in the lateral hypothalamic area (LHA) in goats. Seven male Japanese Saanen goats were used in the experiment. The animals were fed twice daily, once in the morning (1000 to 1200) with 1.5 kg of roughly crushed alfalfa hay cubes, and once in the afternoon (1600 to 1800) with 200 g of commercial ground concentrate feed. The animals were allowed free access to drinking water. In this study, the animals were surgically operated on to position the recording electrode in the LHA. Recordings of SUA were carried out continuously over a 2.25-h period beginning 15 min prior to the commencement of morning feeding. The eating rates of crushed alfalfa hay cubes were highest 10 min after feeding commencement, but decreased sharply by the time 40 min had elapsed. The cumulative feed intake after the completion of the 2-h feeding period was 1164 +/- 38 g. The cumulative water intake upon the conclusion of the 2-h feeding period was 2422 +/- 107 mL. This study recorded 31 units, of which five showed a response to feeding and altered their firing rates. In response to a sharp increase in eating rates, all five units increased their firing rates to a level higher than that of prefeeding (P < 0.05). As the animals reached a level of satiety (eating rates declined to very low levels), firing of units I and II stopped completely, while the firing rates of units III, IV, and V decreased. Examination of a serial histological section confirmed that the five units in which changes in firing rates with feeding were observed were all located in the dorsolateral hypothalamic area close to the fornix. The LHA neurons recorded in this experiment characteristically showed neuronal activity increases at high levels of feeding, but decreases at low levels. The results suggest that there are cells located in the LHA of goats that are active in the physiological regulation of hay (dry forage) intake.

Ameliorative effects of a cognitive enhancer, T-588, on place learning deficits induced by transient forebrain ischemia in rats.

In the present study, we investigated the effect of (1R)-1-benzo[b]thiophen-5-yl-2-[2-(diethylamino)ethoxy]ethan-1-ol hydrochloride (T-588), a newly synthesized cognitive enhancer, on place learning deficits in rats with damage selective to the hippocampal CA1 subfield induced by transient forebrain ischemia. Three weeks after the ischemic insult, T-588 was daily administered (0.3 or 3.0 mg/kg/day po). Place learning was tested in a task in which the rat was required to alternatively visit two places located diametrically opposite each other in an open field. The ischemic rats without the treatment of T-588 displayed severe learning impairment in this task; their performance level was significantly inferior to that of the sham-operated rats. The treatment of T-588 improved dose-dependently the task performance in ischemic rats, although no apparent protective effects on ischemic damage were found histologically. These results suggested that T-588 has ameliorative effects on learning deficits induced by brain ischemia, which could be produced through enhancement of residual cognitive functions.

Effects of T-588, a cognitive enhancer compound, on synaptic plasticity in the dentate gyrus of freely moving rats.

(1R)-1-benzo [b] thiophen-5-yl-2-[2-(diethylamino) ethoxy] ethan-1-ol hydrochloride (T-588) is a compound for the treatment of neurodegenerative disorders, including Alzheimer's disease and cerebrovascular diseases. T-588 reportedly alleviates learning and memory deficits in animal models of dementia. In the present study, we investigated the effects of T-588 on the induction and decay of long-term potentiation (LTP) and on the responses to paired-pulse (pp) stimulation in freely moving rats. Perforant path-evoked field potentials were recorded in the dentate gyrus by chronically implanted electrodes. LTP was induced by high-frequency stimulation 30 min after oral administration of T-588 (0.3 or 3 mg/kg). T-588 significantly augmented the increase in population spike amplitude and field excitatory postsynaptic potential slope after LTP induction. T-588 also prolonged the decay of augmented population spike amplitude, but had no significant effect on the response to pp stimulation. These results suggest that T-588 facilitates long-term synaptic plasticity, but not short-term synaptic plasticity in the dentate gyrus of freely moving rats. The effect of T-588 on long-term synaptic plasticity may contribute to the alleviation of learning and memory dysfunction seen in animal models.

Comparison of medial and lateral septal neuron activity during performance of spatial tasks in rats.

The septal complex, having close and reciprocal connections with the hippocampus, is known to play an important role in learning and memory. Anatomically, the septal complex is divided into the medial and lateral areas (MS and LS). In the present study, in order to elucidate functional differences between the MS and LS, we recorded single unit activity in the MS or LS and electroencephalogram (EEG) in the hippocampus simultaneously while the rats performed the following 2 spatial tasks in an open-field chamber. In task 1, the rat received rewarding intracranial electrical stimulation (ICES) when it entered in a reward place that was set randomly in the open field in each trial. In task 2, the rat received rewarding ICES when it alternately visited two fixed reward places in the open field. Unit activity was analyzed in relation to the pattern of hippocampal EEG, and rat's location, locomotion direction and locomotion speed in the spatial tasks. A total of 47 neurons were recorded in the septal complex (MS, 19; LS, 28). The majority of neurons with activity correlated with hippocampal EEG were found in the MS (14/19). All of the neurons with place-related activity (an increase in unit activity when the rat was in a specific location in the open field) were found in the LS (n = 15). The majority of neurons with direction-related activity were found in the LS (18/23). Twenty-one neurons displayed speed-related activity (MS, 9; LS, 12). The present results indicate that (1) the MS is directly involved in the formation and control of hippocampal EEG patterns, and (2) the LS is important for the processing and integration of spatial information in the environment.