Brain Research, 537 (1990) 293-297 293 Elsevier BRES 24434 Short Communications Long-term potentiation-induced synaptic changes in hippocampal dentate gyrus of rats with an inborn low or high learning capacity Ratil A. G6mez 1, Lucas D. Pozzo Miller 2'*, Augustin Aoki 2 and Oscar A. Ramirez 1 1Departamento de Farmacolog[a, Facultad de Ciencias Qu[micas, Universidad Nacional de C6rdoba, C6rdoba (Argentina) and ZCentro de Microscop[a Electr6nica, Facultad de Ciencias Mddicas, Universidad Nacional de C6rdoba, C6rdoba (Argentina) (Accepted 4 September 1990) Key words: Learning capacity; Dentate gyrus; Synaptic change; Hippocampal slice; Long-term potentiation Structural changes induced by high frequency (I-IF) stimulation on granule cells of the hippocampal dentate gyrns of rats with inborn high (HP) and low (LP) learning capacity was examined in this study. Two types of axodendritic synapses were processed morphometrically; the axonal bouton on dendritic shafts and those making contact through dendritic spines. The occurrence of granule cell spine synapses on LP rats before tetanus is less than the one in control animals. However, after long-term potentiation (LTP) produced by I-IF stimulation the number of spine synapses decreased, as happened in the control rats. Moreover, the number of granule cells shaft synapses counted on LP rats, before tetanus is less than the one on control rats, and after LTP this number increased greatly. There was no change in the number of granule cell shaft synapses in HP rats before and after LTP. LP rats which did not show LTP in spite of I-IF stimulation did not show changes in the number of spine and shaft synapses. From these results we can conclude that: (1) the great hippocampal synaptic plasticity observed in HP rats compared to LP rats can be attributed, at least in part, to the increased number of spine and shaft synapses observed in HP rats; (2) the minor number of spine and shaft synapses in LP rats may account for the impossibility to obtain LTP after I-IF stimulation in these animals. Long-term potentiation (LTP) is characterized by a long-lasting (hours-days) increase in synaptic efficacy produced by high-frequency afferent stimulation to either the hippocampal granule or a pyramidal cell 6'7. This phenomenon has been proposed as a model for studies of the SNC plasticity 1'19'21'28 and it is also a useful model to test learning and memory 4. A number of studies sug- gested that the primary site of LTP is postsynaptic 5"2°, and several postsynaptic ultrastructural correlates of LTP were described s,9,1s. There is also some evidence of a presynaptic contribution to hippocampal LTP 2,5,H. Different lines of evidence suggested a relationship between hipp0campal synaptic plasticity and learning 22- 25,32. Previous results from this laboratory showed a good correlation between the hippocampal synaptic plasticity and the performance in a shuttle box avoidance para- digm 29. Moreover, rats with an inborn low performance in a shock-induced escape behavior revealed a greater threshold to generate LTP in comparison to rats with an inborn high performance response in a shuttle box avoidance paradigm 3°. In the present investigation, a morphometric synapse analysis on the hippocampal granule cell was carried out at an ultrastructural level in both HP and LP rats under basal conditions, and the structural changes observed before and after LTP on granule cell synapses were related with the different hippocampal synaptic plasticity exhibited in HP and LP rats 30. Male albino rats, 6-9 weeks old, were used. They were descendants of HP or LP rats. These strains were inbred for many generations at the time of this study a°. High performance rats were defined as those that made 70% or more conditioned responses (CRs) while LP rats were those with a 15% or less CRs in the shuttle box avoidance paradigm 12. Electrophysiological experiments were conducted in a hippocampal slice preparation in vitro, as essentially described by Yamamoto et al. 33. To prevent circadian variations and non-specific stress 1° the animals were killed with a blow to the neck between 11.00 and 12.00 h. Transverse hippocampal slices of approximately 400/~m thick were placed in a recording chamber perfused with a standard salt solution 33 saturated with 95% 0 2 and 5% CO 2. The perfusion rate was 2-3 ml/min; the tempera- ture of the bathing solution was 30 °C. Under visual control, a stimulating electrode made of two twisted wires was placed in the perforant path (PP). This electrode was insulated except for the cut end (diameter * Present address: Departments of Neurology and Neuroseiences, School of Medicine, E-604, Case Western Reserve University, 2119 Abington Road, Cleveland, 44106 OH, U.S.A. Correspondence: O.A. Ramfrez, Departamento de Farmacologia, Facultad de Cieneias Qufmicas, Universidad Nacional de C6rdoba, Sueursal 16, C.C. 61, 5016 C6rdoba, Argentina. 0006-8993/90/$03.50 ~) 1990 Elsevier Science Publishers B.V. (Biomedical Division)