J. Leiva

Copper suppresses hippocampus LTP in the rat, but does not alter learning or memory in the morris water maze.

The objective of our study was to determinate the effect of copper on long-term potentiation (LTP) in hippocampus slices and a learning test in the Morris Water Maze (MWM). A group of adult Wistar rats received intraperitoneal (ip) injections of 1 mg/kg of CuSO(4) dissolved in saline for 30 consecutive days (Cu.R). A group of control rats (Sal.R), received saline by the same routes and duration. After this period, every individual of both groups was submitted to learning in MWM. Once the learning was completed, the LTP was studied in slices of hippocampus of both groups. The statistical assessment shows that the rats in both groups did not show significant differences in their progressive learning, notwithstanding that group Cu.R had 14.2 times more copper in their hippocampus and 16.7 times more in the visual cortices than in those of group Sal.R. On the other hand, the neurons of CA1 in hippocampus slices of Sal.R showed a significant development of LTP, but this was not observed in group Cu.R. In a second situation, 13 rats received training in MWM. Then, a group of 6 animals were injected with copper i.p. at the dose and time previously described. The 7 other animals were administered saline. Afterward, both groups were retrained in the MWM. The results obtained in Cu.R were similar to those obtained in Sal.R. Both groups maintained the concentrations of copper in the hippocampus indicated above, nonetheless, only the hippocampus slices of Cu.R did not show LTP. The spatial learning behavior of the rats was not affected by high copper concentration.

Interference of chronically ingested copper in long-term potentiation (LTP) of rat hippocampus

The objective of our study was to find the evidence of copper interaction in LTP, motivated by copper involvement in neurodegenerative illness, like Parkinson, Alzheimer and Amyotrophic Lateral Sclerosis, and we initiated the study of this element in the LTP. For this purpose we used hippocampus slices of rats chronically consuming copper dissolved in water (CuDR; n=26) and non-copper-consuming rats (CR; n=20). The CuDR rats received 8--10 mg/day during 20--25 days. Electrophysiological tests showed absence of LTP in CuDR slices, contrary to CR slices. The stimulus-response test applied before and after LTP showed significant increases of synaptic potential in the CR group. This did not occur in the CuDR group, except for the initial values, which probably seem associated to an early action of copper. The paired-pulse (PP) test, applied to CR and CuDR prior to tetanic stimulation, showed a significant reduction in PP, for the 20-, 30- and 50-ms intervals in CuDR. At the end of the experiments, copper concentration was 54.2 times higher in CuDR slices, compared to the concentration present in CR slices. Our results show that copper reduces synaptic sensibility and also the facilitation capability. These effects represent a significant disturbance in the plasticity phenomenon associated with learning and memory.

Simultaneous unitary neuronal activity in both superior colliculi and its relation to eye movements in the cat

The analysis of simultaneous unitary neuronal activity related to eye movement and recorded in both superior colliculi has shown a mirror-functioning image. Increase of the frequency discharge in a collicular unit, was associated with a decrease of the frequency discharge in the contralateral superior colliculus unit. This unitary neuronal reciprocal behaviour was observed each time a horizontal or oblique eye movement was produced. It is possible that this reciprocal functioning between neurones in both superior colliculi could exert an important influence on oculomotor brainstem structures. These results give a better idea of the role played by both superior colliculi in the control of conjugate eye movements.

Output pathway for turning behavior from the neostriatum and substantia nigra in cats.

The goal of the present work was to study the output pathway of the information for turning behavior originating in the striatum and coursing through the substantia nigra pars reticulata (SNR). In 45 adult cats distributed in 3 groups, Ni-Cr electrodes were implanted in the caudate nucleus and substantia nigra pars reticulata and depending on the animal group in the superior colliculus (SC), nucleus ventralis lateralis/nucleus ventralis medialis (VL/VM) complex or nucleus tegmenti pedunculopontinus (TPP) of one cerebral hemisphere. The threshold current required to evoke turning behavior was determined in each animal for each implantation site. An electrolytic lesion of the superior colliculus, the VL/VM complex or the nucleus tegmenti pedunculopontinus was carried out in each group of cats. The effects of the lesions on behavior and on the electrical threshold currents were determined and compared with the prelesion values. Finally the extent of the lesions and electrode positions were analyzed. The results show that the substantia nigra pars reticulata is the structure with the lowest thresholds for turning and that the superior colliculus appears to be more relevant for carrying the information for turning than either the VL/VM complex or the nucleus tegmenti pedunculopontinus.

Correlation between pulvinar-lateralis posterior complex unit activity and eye movements in the cat

In 15 encéphale isolé cats, 130 units were recorded in the pulvinar-lateralis posterior complex (P-LP); 19 units responded in relation to horizontal eye movements (15%), 9 of which discharged when ipsiversive movements were recorded and the remaining 10 to contraversive movements. Three units discharged during spontaneous nystagnoid eye movement. All units always responded after initiation of the eye movement, with a latency range between 50 and 250 ms. The eye movement-related units were preferentially located (80%) in the border between the pulvinar and the lateralis posterior complex. Our results show the presence of eye movement-related units in the cats P-LP, and their probable participation in ocular motility.

Study of the morphological, electrophysiological and behavioral effects of unilateral kainic acid injection into the cat's substantia nigra.

Morphological, electrophysiological and behavioral studies were carried out in cats after unilateral kainic acid injection in the substantia nigra. A forced contralateral head turning and compulsive circling was observed after surgery. Fifteen days after, when asymmetry disappeared, apomorphine induced an ipsilateral head and body turning, that was blocked by haloperidol. The percentage of turning, after electrical stimulation in the superior colliculus or pulvinar-lateralis posterior complex, was affected by substantia nigra lesion. This work demonstrates that the nigro-pulvinar-lateral posterior and the nigrotectal projection modulate the capability of electrical stimulation of the target structures to elicit turning, and after unilateral substantia nigra lesion, two opposite directions of asymmetry appear, which are time-dependent and modulated by different neurotransmitters.

Effects of superior colliculus electrolytic lesion on eye movements evoked through electrical stimulation of the pulvinar-lateralis posterior complex

Abstract In 27 encephale isole cats, electrical stimulation of the pulvinar-lateralis posterior nucleus complex (P-LP) evoked oblique conjugate saccadic eye movements, with latencies of 60 to 90 ms and stimulus thresholds of 200 to 300 μA. Unilateral superior colliculus electrolytic lesion suppressed the eye movements induced by electrical stimulation of the ipsilateral P-LP, even with stimuli three to four times higher than threshold. The contralateral P-LP maintained its capacity to induce eye movement. A motor deficit was observed in the eye ipsilateral to the damaged superior colliculus. Electrical stimulation with 1 to 2 mA of the cerebral cortex receiving afferent projections from the P-LP induced horizontal eye movements with latencies of 130 to 150 ms. These results confirm the P-LP participation in oculomotility and we postulate that the ocular P-LP signal output travels through the ipsilateral superior colliculus.

Extracellular unit responses in the pulvinar-lateral posterior complex of the cat through electrical stimulation of substantia nigra reticulata and lateralis

Extracellular single-unit responses of neurons in the ipsilateral pulvinar-lateral posterior complex were recorded in 10 encéphale isolé cats with stimulating electrodes implanted in the substantia nigra pars reticulata and pars lateralis. Fifteen percent of 101 pulvinar-lateral posterior complex thalamic neurons increased their spike discharges when the substantia nigra was stimulated and none decreased its activity. The excitatory effect of this stimulation is discussed in relation to the eventual excitatory or inhibitory character of the efferent projection from the substantia nigra pars reticulata and lateralis to the pulvinar-lateral posterior complex.