Biomedical subjects

B Sacchetti

Publications and source records attributed to B Sacchetti.

21 records · Page 2Linked to original sources

PubMed1997

Analysis of mnemonic processing by means of totally reversible neural inactivations.

The irreversible lesions technique precludes the analysis of the possibly critical role played by discrete brain sites in the several distinct stages of mnemonic processing (acquisition, consolidation, retrieval) during which these may be specifically but transiently active. On the contrary, the reversible functional inactivation techniques, by means of stereotaxic local microinjection of active compounds, make it possible to suppress the neuronal function of a discrete volume of nervous tissue, for a pre-determined time, with the assurance of complete functional recovery within a known duration. This technique makes it possible to block the neural activity of a chosen neural site at a given stage of memory processing without any interference with the function of the same structure either during earlier or later stages of the same process. Thus, the reversible ablation results may provide information not only on the qualitative topographical but also on the quantitative temporal dimension of learning and memory. The technique employed to cause totally reversible neural inactivation is detailed. The employment of several agents to obtain functional inactivation is discussed. Of these, perhaps the safest and most manageable is tetrodotoxin when a fairly long functional inactivation (e.g., 1 h) is desired. The effects of a reversible inactivation can be quite easily and accurately assessed by observing the severity of the amnesic disruption, if any, of a conditioned response. In order to do this as well as possible, it is advantageous to employ a very simple behavioral paradigm. The passive avoidance response in the light-dark box apparatus fulfills this requirement. Moreover, this paradigm, being one-trial, provides the necessary condition of a single well-defined temporal beginning. The present protocol has been successfully employed in learning and memory research, to assess when the functional integrity of a given neural structure is necessary in order that a conditioned response may be acquired, consolidated or retrieved. The employment of this protocol in relation to the intrinsic functional characteristics of a given subcortical neural site is discussed.

Animals↗

PubMed1996

Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat's passive avoidance response: a tetrodotoxin functional inactivation study.

By means of local administration of tetrodotoxin (TTX) fully reversible functional inactivation of rat's dorsal hippocampus (DH) was obtained in order to define the role of this structure in the memorization of a conditioned passive avoidance response (PAR). In Experiment 1, on permanently cannulated animals, TTX (10 ng in 1.0 microliter saline) or saline (1.0 microliter) was injected uni- or bilaterally in the DH, respectively 1 h before PAR acquisition, immediately after PAR acquisition, and 1 h before PAR retrieval, always performed 48 h after the acquisition trial. It was shown that both pre-acquisition and pre-retrieval DH uni- or bilateral blockades were followed by significant PAR retention impairment, while in post-acquisition only the bilateral blockade determined PAR retention impairment. In Experiment 2, on three different groups of rats, TTX (10 ng in 1 microliter) saline) was bilaterally administered, under general ketamine anesthesia (100 mg/kg), into the DH at different post-acquisition delays (0.25, 1.5, 6 h). Retrieval testing, 48 h after treatment, showed that post-acquisition bilateral DH blockade caused PAR impairment only when performed 0.25 or 1.5 h after acquisition. The results indicate a well defined mnemonic role of DH during the acquisition, consolidation and retrieval of PAR engram. The experimental evidence is discussed in relation to other reports and to DH connectivity with the medial septal area and the amygdala.

Animals↗

PubMedDate not supplied

The presence of astrocytes enhances beta amyloid-induced neurotoxicity in hippocampal cell cultures.

A characteristic feature of neuritic plaques in Alzheimer's disease is represented by the presence of activated astrocytes, surrounding dystrophic neurons and beta-amyloid deposition. To explore the role of astrocytes in in vitro beta-amyloid neurotoxicity, we studied the effect of beta-amyloid treatment in hippocampal neurons in two different cell models: pure cultures, where neurons were grown in absence of astrocytes and mixed cultures, where neurons were seeded on a confluent layer of astrocytes. We evaluated two characteristic aspects of in vitro beta-amyloid neurotoxicity: reduction of cell viability and degeneration of the neuritic tree. We demonstrated that neurons growing on astrocytes were more prone to the detrimental effect of the amyloid peptide, with respect to neurons grown in absence of the glial component. Our results support the hypothesis that beta-amyloid-astrocyte interaction can adversely condition neurons and contribute to neuronal damage in Alzheimer's disease.

Amyloid beta-Peptides↗