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Enhancement of hippocampal field potentials in rats exposed to a novel, complex environment
Brain Research, 339 (1985) 361-365 Elsevier
361
BRE 20956
Enhancement of hippocampal field potentials in rats exposed to a novel, complex environment PATRICIA E. SHARP, BRUCE L. McNAUGHTON and CAROL A. BARNES Department of Psychology, University of Colorado, Boulder, CO 80309 (U.S.A.)
(Accepted March 12th. 1985) Key words: hippocampus - - synaptic enhancement - - environmental enrichment - - spatial learning - - field potential - population spike - - perforant path
The hippocampus plays a crucial role in place learning in rodents and also exhibits a long-term enhancement of synaptic strength and postsynaptic excitability following electrical stimulation of its principal afferents. In the present report we suggest that these two observations may be related, by demonstrating an increase in synaptic and postsynaptic field potential amplitudes resulting from exposure to a spatially complex environment. Most theoretical accounts of the biological basis of learning involve the notion that the synaptic connection between neurons is strengthened through use 9,1°. This means that if a particular synapse is active during a learning task, then its functional strength will increase (under certain conditions) so that on subsequent occasions the learned behavior will be more readily generated. Empirical evidence for this postulate is sparse, however, particularly in vertebrates. This study was carried out on the rat hippocampal formation, which seems to be involved in learning of tasks which require navigation through complex environments 13. Moreover, this system has been shown to exhibit a long-term enhancement (LTE) of synaptic strength following high frequency stimulation of its afferent fibersS.6. (This p h e n o m e n o n is also known in the literature as long-term potentiation, or LTP, but is referred to here as L T E for reasons outlined by McNaughtonll.) This L T E has many of the logical properties required on a priori grounds by attempts to construct models of associative learning based on synaptic strengtheningl2. The central question addressed by this study is whether a similar form of plasticity can be induced through behavioral, rather than artificial stimulation. This was examined by observing the effect of
exposure to a spatially complex environment on the synaptic field potential and postsynaptic population spike recorded from the dentate gyrus of the hippocampal formation. These field potentials were evoked by single perforant path test stimuli in animals with chronically implanted electrodes. Electrically induced LTE eventually decays with a time constant of about 30 days3. Therefore animals were housed in an environment poor in spatial information for an extended period prior to the experimental manipulation. It was presumed that any natural L T E in the system would decay during this time, thus improving the likelihood of detecting an effect of the new environment. Five male, Holtzman rats (462-615 g) were chronically implanted with stimulating and recording electrodes in the perforant path and the ipsilateral dentate gyrus respectively 2. Following surgery, all animals were housed singly in 34 x 23 cm laboratory cages in a dimly lit, quiet room (lights out between 19.00 and 07.00 h) for a period of at least 1 month prior to the beginning of the actual experiment. Population responses from the granule cells were evoked by single stimulus pulses delivered to the perforant path. Examples of these are shown in Fig. 2A. The amplitude of the EPSP was measured as the vertical distance between two points at a fixed latency from
Correspondence: P. E. Sharp, Department of Psychology, University of Colorado, Campus Box 345, Boulder, CO 80309, U. S. A.
0006-8993/85/$03.30 © 1985 Elsevier Science Publishers B.V. (Biomedical Division)
362 the stimulus artifact, on the rising phase of the EPSP. The population spike was measured as the vertical distance between the initial negative deflection of the waveform and the point of maximum negativity. This value was then approximately corrected for superimposition on the EPSP, Population responses were taken during daily recording sessions consisting of 40 single test pulses delivered at 0.067 Hz to the perforant path. These sessions were carried out between 07.00 and 09.30 h throughout the experiment. During this time the animals were free to move about in an 18 cm diameter plexiglass chamber, Behavioral observations were made at the time of each stimulus pulse delivery• In this way, any gross behavioral changes induced by the environmental enrichment treatment could be monitored. The behavioral observations were broken down into three categories: (1) exploration (including behaviors such as sniffing, walking and rearing); (2) grooming; and (3) still alertness (animal is motionless, but does not appear to be asleep). After an initial 10 days of baseline testing, during which all animals were housed in the restricted environment, three of the animals were transferred to individual rooms ranging from 104 to 195 ft. 2 filled with boxes, wooden ramps and other surfaces for the animals to run on. They remained in these rooms for the rest of the experiment, except during recording sessions. The control animals remained in their standard cages. Evidence that the experimental animals thoroughly explored their environment was provided by the fact that they collected all the food that was scattered around it, and also by the pattern of droppings. Daily means for the population spike and EPSP for each animal are shown in Fig. 1. There were significant increases in the experimental animals in both the EPSP and spike magnitudes after the initiation of the environmental enrichment treatment. These increases developed over a period of several days. The relative increases in spike magnitude were larger than those for the EPSP. This is similar to what is seen in much of the LTE literature1,5.% and may reflect an increased postsynaptic excitability which may be dissociable from synaptic LTE. The EPSP change observed here was rather small, and needs to be viewed with some caution since the field EPSP can be modulated by a variety of influences other than LTE, such as the tonic level of hyperpolarization. The con-
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Fig. 1. Daily means of population spike (left column) and field EPSP (right column) for individual experimental (El-E3) and control (CI-C2) animals. Arrow indicates time of transfer of experimental animals to enriched environmentl A significant, non-linear change in both the EPSP and spike measures was induced by the enrichment treatment. trol animals' data showed no such discrete transitions• The statistical significance of the non-linear change in the experimental animals' spike and EPSP amplitudes was assessed by performing serial correlations on the residuals of the linear regression lines fit to the data points for the individual animals. Even with the small number of animals employed here, the mean between groups difference in correlation coefficients for both the spike and the EPSP were significantly different (tEesP = 38.09, P < 0:005; tspik e 32.5, P < 0•005). The results for the behavioral observations made during the daily recording sessions are shown in Fig. 2B. Only the results for the exploration category have been displayed. The experimental group showed a dramatic decline in amount of exploratory
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Fig. 2. A: two superimposed granule cell evoked responses from a representative experimental animal. Trace 1 is from day 1 of the experiment during baseline testing. Trace 2 is from day 14, after environmental enrichment had begun. B: percent of the 40 daily observations during which the animals from each group showed exploratory activity. C and D: normalized EPSP amplitude group m e a n s for the control (C) and experimental (D) groups. E a c h day's data has been broken up into three m e a n s , according to which behavior was observed at the time of stimulus delivery ( 0 , exploratory behavior; II, still alertness; and A , grooming), E and F spike amplitude data are similarly normalized and divided according to behavioral category.
364 activity, starting the day after initiation of the enrichment treatment. This decrease in exploratory activity was compensated by proportional increases in the grooming and still alertness categories. A number of hypotheses might explain this effect, an obvious possibility being fatigue from the increased exploratory activity in the novel environment. Winson and Abzug 16 have demonstrated that an animal's momentary behavioral state can affect the magnitude of its evoked granule cell response. Thus, the change in the experimental group EPSP and spike magnitude might have been related simply to the changed behavior during the time of stimulus delivery. In order to assess this possibility the data for each group were divided into three categories according to the animals' behavior at the time of stimulus delivery. Separate means were calculated for responses which were evoked during each of grooming, exploration and still alertness. These data are shown in Fig. 2C-F. It can be seen that increases in physiological response magnitude were observed within each behavioral category. Thus, changes in behavior cannot account for these increases. This dissociation of behavior and response change is further supported by the fact that the full extent of the change in the behavioral measure was seen after the first day in the new environment, whereas the evoked responses reached their maximum only after several days. There are several possible explanations for the gradual development over several days of the spike and EPSP effects found here, including the successive exploration of different parts of the environments or the possibility that repeated exposure to the same environmental stimuli may be necessary to saturate the effect. We have examined the effects of a successive exposure to a second novel environment in one animal. A further increase in the evoked response amplitude was observed. It will be noted that the spike change for E1 (Fig. 1) shows a tendency to decay even while the animal is still in the enriched environment. A similar tendency was found in the data of the animal which was exposed to a second novel environment. While this observation requires further verification, it suggests that the response change may decay as the animal becomes fully familiar with its surroundings. The findings presented here indicate that an in-
crease in evoked population spike and population EPSP magnitude resulted from housing animals m an enriched environment. These data are complementary to those of others', 15 who have shown a wide variety of structural changes in neocortex and hippocampus as a result of environmental enrichment treatments. The present findings demonstrate that there is a functional as well as morphological component to these changes. The paradigm used here can be contrasted to that of studies which have examined increases in hippocampal activity during conditioning4.7,J4,17~ In these studies, recordings were made during the actual conditioning session, usually during presentation of the conditioning stimulus. Such studies usually show an increase in hippocampal responsiveness to the conditioning stimulus which develops over the course of conditioning. One drawback to these studies is that in most cases (with the exception of Weisz i7) they have not examined hippocampal cell responses to a known and constant amount of afferent input (such as is provided by the constant perforant path stimulus pulses in this study). That is, the stimulus is presented externally to the animal and thus is processed through many levels of the nervous system before reaching the hippocampal formation. Thus, increases in hippocampal activity could be reflecting any of a wide range of possible changes which have taken place elsewhere in the system. Also, such studies do not make it clear whether any synaptic changes which might be present would persist outside of the conditioning situation itself. That is, they may be dependent on a transitory state induced in the presence of the conditioning treatment. In contrast, in the present study, physiological recording always took place in a room separate from the one in which the change was induced. The present results demonstrate that exposure to a spatially complex environment can alter the synaptic input/output relations between perforant path afferents and dentate granule cells. This, in turn, provides the possibility that behaviorally relevant information about such environments is actually coded by these changes. While the phenomenon found here appears similar to that of artificially induced LTE, it remains to be demonstrated conclusively that a common mechanism is involved. If this can be shown, however, then further study of LTE may provide an ex-
365 t r e m e l y v a l u a b l e t o o l for i n v e s t i g a t i o n of the basic
AG03376-01) and the N I N C D S (1 R01 NS2033101).
p r o p e r t i e s of m e m o r y s t o r a g e in t h e n e r v o u s system.
W e t h a n k D r . S. K. Sharpless for p r o g r a m m i n g assistance and Ms. B e e P e t e r s o n for m a n u s c r i p t p r e p a r a -
S u p p o r t e d by r e s e a r c h grants f r o m the N I A (1 R01
1 Andersen, P., Sundberg, S. H., Sveen, O., Swarm, J. W. and Wigstrom, H., Possible mechanisms for long-lasting potentiation of synaptic transmission in hippocampal slices from guinea-pigs, J. Physiol. (Lond.), 302 (1980) 463-482. 2 Barnes, C. A., Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat, J. comp. Physiol. Psychol., 93 (1979) 74-104. 3 Barnes, C. A. and McNaughton, B. L., Spatial memory and hippocampal synaptic plasticity in senescent and middle-aged rats. In D. Stein (Ed.), The Psychobiology of Aging: Problems and Perspectives, Elsevier, Amsterdam, 1980, pp. 253-272. 4 Berger, T. W., Alger, B. E. and Thompson, R. F., Neuronal substrates of classical conditioning in the hippocampus, Science, 192 (1976) 483-485. 5 Bliss, T. V. P. and Gardner-Medwin, A. R., Long-lasting potentiation of synaptic transmission in the dentate area of the unanaesthetized rabbit following stimulation of the perforant path, J. Physiol. (Lond.), 232 (1973) 357-374. 6 Bliss, T. V. P. and Lomo, T., Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path, J. Physiol. (Lond.), 232 (1973) 331-356. 7 Deadwyler, S. A., West, M. and Lynch, G., Synaptically identified hippocampal slow potentials during behavior, Brain Research, 161 (1979) 211-225. 8 Fiala, B. A., Joyce, J. N. and Greenough, W. T., Environmental complexity modulates growth of granule cell dendrites in developing but not adult hippocampus of rats, Exp. Neurol., 59 (1978) 372-383.
tion.
9 Hebb, D. O., The Organization of Behavior, Wiley, New York, 1949. 10 Marr, D., A theory of cerebellar cortex, J. Physiol. (Lond.), 202 (1969) 437-470. 11 McNaughton, B. L., Long-term synaptic enhancement and short-term potentiation in rat fascia dentata act through different mechanisms, J. Physiol. (Lond.), 324 (1982) 249-262. 12 McNaughton, B. L., Activity dependent modulation of hippocampal synaptic efficacy; some implications for memory processes. In W. Seifert (Ed.), The Neurobiology of the Hippocampus, Academic Press, New York, 1983, pp. 233-252. 13 O'Keefe, J. and Nadel, L., The Hippocampus as a Cognitive Map, Oxford University Press, London, 1978. 14 Patterson, M. M., Berger, T. W. and Thompson, R. F., Neuronal plasticity recorded from cat hippocampus during classical conditioning, Brain Research, 163 (1979) 339-343. 15 Rosenzweig, M. R., Krech, D., Bennett, E. L. and Diamond, M. C., Effects of environmental complexity and training on brain chemistry and anatomy: a replication and extension, J. comp. Physiol. Psychol., 55 (1962)429-437. 16 Winson, J. and Abzug, C., Gating of neuronal transmission in the hippocampus: efficacy of transmission varies with behavioral state, Science, 196 (1977) 1223-1225. 17 Weisz, D. J., Activity of the dentate gyrus during nictitating membrane conditioning in the rabbit. In C. D. Woody (Ed.), Conditioning: Representation of Involved Neural Functions, Advances in Behavioral Biology, 26, Plenum Press, New York, 1982, pp. 131-146.
361
BRE 20956
Enhancement of hippocampal field potentials in rats exposed to a novel, complex environment PATRICIA E. SHARP, BRUCE L. McNAUGHTON and CAROL A. BARNES Department of Psychology, University of Colorado, Boulder, CO 80309 (U.S.A.)
(Accepted March 12th. 1985) Key words: hippocampus - - synaptic enhancement - - environmental enrichment - - spatial learning - - field potential - population spike - - perforant path
The hippocampus plays a crucial role in place learning in rodents and also exhibits a long-term enhancement of synaptic strength and postsynaptic excitability following electrical stimulation of its principal afferents. In the present report we suggest that these two observations may be related, by demonstrating an increase in synaptic and postsynaptic field potential amplitudes resulting from exposure to a spatially complex environment. Most theoretical accounts of the biological basis of learning involve the notion that the synaptic connection between neurons is strengthened through use 9,1°. This means that if a particular synapse is active during a learning task, then its functional strength will increase (under certain conditions) so that on subsequent occasions the learned behavior will be more readily generated. Empirical evidence for this postulate is sparse, however, particularly in vertebrates. This study was carried out on the rat hippocampal formation, which seems to be involved in learning of tasks which require navigation through complex environments 13. Moreover, this system has been shown to exhibit a long-term enhancement (LTE) of synaptic strength following high frequency stimulation of its afferent fibersS.6. (This p h e n o m e n o n is also known in the literature as long-term potentiation, or LTP, but is referred to here as L T E for reasons outlined by McNaughtonll.) This L T E has many of the logical properties required on a priori grounds by attempts to construct models of associative learning based on synaptic strengtheningl2. The central question addressed by this study is whether a similar form of plasticity can be induced through behavioral, rather than artificial stimulation. This was examined by observing the effect of
exposure to a spatially complex environment on the synaptic field potential and postsynaptic population spike recorded from the dentate gyrus of the hippocampal formation. These field potentials were evoked by single perforant path test stimuli in animals with chronically implanted electrodes. Electrically induced LTE eventually decays with a time constant of about 30 days3. Therefore animals were housed in an environment poor in spatial information for an extended period prior to the experimental manipulation. It was presumed that any natural L T E in the system would decay during this time, thus improving the likelihood of detecting an effect of the new environment. Five male, Holtzman rats (462-615 g) were chronically implanted with stimulating and recording electrodes in the perforant path and the ipsilateral dentate gyrus respectively 2. Following surgery, all animals were housed singly in 34 x 23 cm laboratory cages in a dimly lit, quiet room (lights out between 19.00 and 07.00 h) for a period of at least 1 month prior to the beginning of the actual experiment. Population responses from the granule cells were evoked by single stimulus pulses delivered to the perforant path. Examples of these are shown in Fig. 2A. The amplitude of the EPSP was measured as the vertical distance between two points at a fixed latency from
Correspondence: P. E. Sharp, Department of Psychology, University of Colorado, Campus Box 345, Boulder, CO 80309, U. S. A.
0006-8993/85/$03.30 © 1985 Elsevier Science Publishers B.V. (Biomedical Division)
362 the stimulus artifact, on the rising phase of the EPSP. The population spike was measured as the vertical distance between the initial negative deflection of the waveform and the point of maximum negativity. This value was then approximately corrected for superimposition on the EPSP, Population responses were taken during daily recording sessions consisting of 40 single test pulses delivered at 0.067 Hz to the perforant path. These sessions were carried out between 07.00 and 09.30 h throughout the experiment. During this time the animals were free to move about in an 18 cm diameter plexiglass chamber, Behavioral observations were made at the time of each stimulus pulse delivery• In this way, any gross behavioral changes induced by the environmental enrichment treatment could be monitored. The behavioral observations were broken down into three categories: (1) exploration (including behaviors such as sniffing, walking and rearing); (2) grooming; and (3) still alertness (animal is motionless, but does not appear to be asleep). After an initial 10 days of baseline testing, during which all animals were housed in the restricted environment, three of the animals were transferred to individual rooms ranging from 104 to 195 ft. 2 filled with boxes, wooden ramps and other surfaces for the animals to run on. They remained in these rooms for the rest of the experiment, except during recording sessions. The control animals remained in their standard cages. Evidence that the experimental animals thoroughly explored their environment was provided by the fact that they collected all the food that was scattered around it, and also by the pattern of droppings. Daily means for the population spike and EPSP for each animal are shown in Fig. 1. There were significant increases in the experimental animals in both the EPSP and spike magnitudes after the initiation of the environmental enrichment treatment. These increases developed over a period of several days. The relative increases in spike magnitude were larger than those for the EPSP. This is similar to what is seen in much of the LTE literature1,5.% and may reflect an increased postsynaptic excitability which may be dissociable from synaptic LTE. The EPSP change observed here was rather small, and needs to be viewed with some caution since the field EPSP can be modulated by a variety of influences other than LTE, such as the tonic level of hyperpolarization. The con-
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Fig. 1. Daily means of population spike (left column) and field EPSP (right column) for individual experimental (El-E3) and control (CI-C2) animals. Arrow indicates time of transfer of experimental animals to enriched environmentl A significant, non-linear change in both the EPSP and spike measures was induced by the enrichment treatment. trol animals' data showed no such discrete transitions• The statistical significance of the non-linear change in the experimental animals' spike and EPSP amplitudes was assessed by performing serial correlations on the residuals of the linear regression lines fit to the data points for the individual animals. Even with the small number of animals employed here, the mean between groups difference in correlation coefficients for both the spike and the EPSP were significantly different (tEesP = 38.09, P < 0:005; tspik e 32.5, P < 0•005). The results for the behavioral observations made during the daily recording sessions are shown in Fig. 2B. Only the results for the exploration category have been displayed. The experimental group showed a dramatic decline in amount of exploratory
363 10o 7
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Fig. 2. A: two superimposed granule cell evoked responses from a representative experimental animal. Trace 1 is from day 1 of the experiment during baseline testing. Trace 2 is from day 14, after environmental enrichment had begun. B: percent of the 40 daily observations during which the animals from each group showed exploratory activity. C and D: normalized EPSP amplitude group m e a n s for the control (C) and experimental (D) groups. E a c h day's data has been broken up into three m e a n s , according to which behavior was observed at the time of stimulus delivery ( 0 , exploratory behavior; II, still alertness; and A , grooming), E and F spike amplitude data are similarly normalized and divided according to behavioral category.
364 activity, starting the day after initiation of the enrichment treatment. This decrease in exploratory activity was compensated by proportional increases in the grooming and still alertness categories. A number of hypotheses might explain this effect, an obvious possibility being fatigue from the increased exploratory activity in the novel environment. Winson and Abzug 16 have demonstrated that an animal's momentary behavioral state can affect the magnitude of its evoked granule cell response. Thus, the change in the experimental group EPSP and spike magnitude might have been related simply to the changed behavior during the time of stimulus delivery. In order to assess this possibility the data for each group were divided into three categories according to the animals' behavior at the time of stimulus delivery. Separate means were calculated for responses which were evoked during each of grooming, exploration and still alertness. These data are shown in Fig. 2C-F. It can be seen that increases in physiological response magnitude were observed within each behavioral category. Thus, changes in behavior cannot account for these increases. This dissociation of behavior and response change is further supported by the fact that the full extent of the change in the behavioral measure was seen after the first day in the new environment, whereas the evoked responses reached their maximum only after several days. There are several possible explanations for the gradual development over several days of the spike and EPSP effects found here, including the successive exploration of different parts of the environments or the possibility that repeated exposure to the same environmental stimuli may be necessary to saturate the effect. We have examined the effects of a successive exposure to a second novel environment in one animal. A further increase in the evoked response amplitude was observed. It will be noted that the spike change for E1 (Fig. 1) shows a tendency to decay even while the animal is still in the enriched environment. A similar tendency was found in the data of the animal which was exposed to a second novel environment. While this observation requires further verification, it suggests that the response change may decay as the animal becomes fully familiar with its surroundings. The findings presented here indicate that an in-
crease in evoked population spike and population EPSP magnitude resulted from housing animals m an enriched environment. These data are complementary to those of others', 15 who have shown a wide variety of structural changes in neocortex and hippocampus as a result of environmental enrichment treatments. The present findings demonstrate that there is a functional as well as morphological component to these changes. The paradigm used here can be contrasted to that of studies which have examined increases in hippocampal activity during conditioning4.7,J4,17~ In these studies, recordings were made during the actual conditioning session, usually during presentation of the conditioning stimulus. Such studies usually show an increase in hippocampal responsiveness to the conditioning stimulus which develops over the course of conditioning. One drawback to these studies is that in most cases (with the exception of Weisz i7) they have not examined hippocampal cell responses to a known and constant amount of afferent input (such as is provided by the constant perforant path stimulus pulses in this study). That is, the stimulus is presented externally to the animal and thus is processed through many levels of the nervous system before reaching the hippocampal formation. Thus, increases in hippocampal activity could be reflecting any of a wide range of possible changes which have taken place elsewhere in the system. Also, such studies do not make it clear whether any synaptic changes which might be present would persist outside of the conditioning situation itself. That is, they may be dependent on a transitory state induced in the presence of the conditioning treatment. In contrast, in the present study, physiological recording always took place in a room separate from the one in which the change was induced. The present results demonstrate that exposure to a spatially complex environment can alter the synaptic input/output relations between perforant path afferents and dentate granule cells. This, in turn, provides the possibility that behaviorally relevant information about such environments is actually coded by these changes. While the phenomenon found here appears similar to that of artificially induced LTE, it remains to be demonstrated conclusively that a common mechanism is involved. If this can be shown, however, then further study of LTE may provide an ex-
365 t r e m e l y v a l u a b l e t o o l for i n v e s t i g a t i o n of the basic
AG03376-01) and the N I N C D S (1 R01 NS2033101).
p r o p e r t i e s of m e m o r y s t o r a g e in t h e n e r v o u s system.
W e t h a n k D r . S. K. Sharpless for p r o g r a m m i n g assistance and Ms. B e e P e t e r s o n for m a n u s c r i p t p r e p a r a -
S u p p o r t e d by r e s e a r c h grants f r o m the N I A (1 R01
1 Andersen, P., Sundberg, S. H., Sveen, O., Swarm, J. W. and Wigstrom, H., Possible mechanisms for long-lasting potentiation of synaptic transmission in hippocampal slices from guinea-pigs, J. Physiol. (Lond.), 302 (1980) 463-482. 2 Barnes, C. A., Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat, J. comp. Physiol. Psychol., 93 (1979) 74-104. 3 Barnes, C. A. and McNaughton, B. L., Spatial memory and hippocampal synaptic plasticity in senescent and middle-aged rats. In D. Stein (Ed.), The Psychobiology of Aging: Problems and Perspectives, Elsevier, Amsterdam, 1980, pp. 253-272. 4 Berger, T. W., Alger, B. E. and Thompson, R. F., Neuronal substrates of classical conditioning in the hippocampus, Science, 192 (1976) 483-485. 5 Bliss, T. V. P. and Gardner-Medwin, A. R., Long-lasting potentiation of synaptic transmission in the dentate area of the unanaesthetized rabbit following stimulation of the perforant path, J. Physiol. (Lond.), 232 (1973) 357-374. 6 Bliss, T. V. P. and Lomo, T., Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path, J. Physiol. (Lond.), 232 (1973) 331-356. 7 Deadwyler, S. A., West, M. and Lynch, G., Synaptically identified hippocampal slow potentials during behavior, Brain Research, 161 (1979) 211-225. 8 Fiala, B. A., Joyce, J. N. and Greenough, W. T., Environmental complexity modulates growth of granule cell dendrites in developing but not adult hippocampus of rats, Exp. Neurol., 59 (1978) 372-383.
tion.
9 Hebb, D. O., The Organization of Behavior, Wiley, New York, 1949. 10 Marr, D., A theory of cerebellar cortex, J. Physiol. (Lond.), 202 (1969) 437-470. 11 McNaughton, B. L., Long-term synaptic enhancement and short-term potentiation in rat fascia dentata act through different mechanisms, J. Physiol. (Lond.), 324 (1982) 249-262. 12 McNaughton, B. L., Activity dependent modulation of hippocampal synaptic efficacy; some implications for memory processes. In W. Seifert (Ed.), The Neurobiology of the Hippocampus, Academic Press, New York, 1983, pp. 233-252. 13 O'Keefe, J. and Nadel, L., The Hippocampus as a Cognitive Map, Oxford University Press, London, 1978. 14 Patterson, M. M., Berger, T. W. and Thompson, R. F., Neuronal plasticity recorded from cat hippocampus during classical conditioning, Brain Research, 163 (1979) 339-343. 15 Rosenzweig, M. R., Krech, D., Bennett, E. L. and Diamond, M. C., Effects of environmental complexity and training on brain chemistry and anatomy: a replication and extension, J. comp. Physiol. Psychol., 55 (1962)429-437. 16 Winson, J. and Abzug, C., Gating of neuronal transmission in the hippocampus: efficacy of transmission varies with behavioral state, Science, 196 (1977) 1223-1225. 17 Weisz, D. J., Activity of the dentate gyrus during nictitating membrane conditioning in the rabbit. In C. D. Woody (Ed.), Conditioning: Representation of Involved Neural Functions, Advances in Behavioral Biology, 26, Plenum Press, New York, 1982, pp. 131-146.