Recent evidence indicates that the activation of a calcium-dependent proteinase, calpain, results in the formation of new glutamate receptors in the hippocampus (Lynch, Halpain, & Baudry, 1982), a brain area commonly thought to play a crucial role in mammalian memory formation. In vitro, this effect is correlated with a long-lasting enhancement of efficacy in synaptic transmission (long-term potentiation, LTP) following brief pulses of electrical stimulation in the hippocampus (Dunwiddie & Lynch, 1979). Because the induction properties of LTP are similar to the behavioral properties of memory, it has been proposed to be the physiological basis of memory (Lynch & Baudry, 1984). If the calcium-dependent activation of calpain is responsible for the induction of LTP and ultimately memory formation, then pharmacologically blocking the calcium-calpain interactions should block those forms of memory dependent on this mechanism.
Three experiments were conducted to assess the effects of leupeptin, a proteinase (calpain) inhibitor on aversively motivated spatial memory in rats. In Experiment One, either leupeptin (8 mg/ml isotonic saline) or isotonic saline was infused continuously into the cerebrospinal fluid, and rats were trained in a one-way avoidance task with one-hour intertrial intervals, three trials per day, for 11 days. Leupeptin significantly impaired rats' acquisition of this task. Experiment Two assessed rats' performance in a win-stay or a win-shift avoidance task, and it was found that rats in the win-shift group learned the task more efficiently. This win-shift avoidance task was then used in Experiment Three to assess the temporal dependence of leupeptin's behavioral effects by introducing a delay of 1 min, 15 min, or 30 min between the information and choice trials. Leupeptin impaired choice performance at the 30 min delay only. In addition, leupeptin significantly impaired previously-acquired avoidance responding. Because a time-dependent memory deficit was observed, these data are considered to be consistent with the biological model of memory formation advanced by Lynch & Baudry (1984), however no adequate explanation of leupeptin's deleterious effects on previously acquired responding presently exists.
","abstract_html":"<p>Recent evidence indicates that the activation of a calcium-dependent proteinase, calpain, results in the formation of new glutamate receptors in the hippocampus (Lynch, Halpain, & Baudry, 1982), a brain area commonly thought to play a crucial role in mammalian memory formation. In vitro, this effect is correlated with a long-lasting enhancement of efficacy in synaptic transmission (long-term potentiation, LTP) following brief pulses of electrical stimulation in the hippocampus (Dunwiddie & Lynch, 1979). Because the induction properties of LTP are similar to the behavioral properties of memory, it has been proposed to be the physiological basis of memory (Lynch & Baudry, 1984). If the calcium-dependent activation of calpain is responsible for the induction of LTP and ultimately memory formation, then pharmacologically blocking the calcium-calpain interactions should block those forms of memory dependent on this mechanism.</p><p>Three experiments were conducted to assess the effects of leupeptin, a proteinase (calpain) inhibitor on aversively motivated spatial memory in rats. In Experiment One, either leupeptin (8 mg/ml isotonic saline) or isotonic saline was infused continuously into the cerebrospinal fluid, and rats were trained in a one-way avoidance task with one-hour intertrial intervals, three trials per day, for 11 days. Leupeptin significantly impaired rats' acquisition of this task. Experiment Two assessed rats' performance in a win-stay or a win-shift avoidance task, and it was found that rats in the win-shift group learned the task more efficiently. This win-shift avoidance task was then used in Experiment Three to assess the temporal dependence of leupeptin's behavioral effects by introducing a delay of 1 min, 15 min, or 30 min between the information and choice trials. Leupeptin impaired choice performance at the 30 min delay only. In addition, leupeptin significantly impaired previously-acquired avoidance responding. Because a time-dependent memory deficit was observed, these data are considered to be consistent with the biological model of memory formation advanced by Lynch & Baudry (1984), however no adequate explanation of leupeptin's deleterious effects on previously acquired responding presently exists.</p>","abstract_has_math":false,"creators":["OTTO, TIMOTHY ANDREW"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Dissertation","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1986,"date_issued":"1986-01-01T08:00:00Z","date_published":"1986-01-01T08:00:00Z","updated_at":"2026-07-24T05:23:21Z","subjects":["Psychology","Psychobiology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholars.unh.edu/dissertation/1497","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["OTTO, TIMOTHY ANDREW"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Psychology","Psychobiology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholars.unh.edu/dissertation/1497"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Recent evidence indicates that the activation of a calcium-dependent proteinase, calpain, results in the formation of new glutamate receptors in the hippocampus (Lynch, Halpain, & Baudry, 1982), a brain area commonly thought to play a crucial role in mammalian memory formation. In vitro, this effect is correlated with a long-lasting enhancement of efficacy in synaptic transmission (long-term potentiation, LTP) following brief pulses of electrical stimulation in the hippocampus (Dunwiddie & Lynch, 1979). Because the induction properties of LTP are similar to the behavioral properties of memory, it has been proposed to be the physiological basis of memory (Lynch & Baudry, 1984). If the calcium-dependent activation of calpain is responsible for the induction of LTP and ultimately memory formation, then pharmacologically blocking the calcium-calpain interactions should block those forms of memory dependent on this mechanism.
Three experiments were conducted to assess the effects of leupeptin, a proteinase (calpain) inhibitor on aversively motivated spatial memory in rats. In Experiment One, either leupeptin (8 mg/ml isotonic saline) or isotonic saline was infused continuously into the cerebrospinal fluid, and rats were trained in a one-way avoidance task with one-hour intertrial intervals, three trials per day, for 11 days. Leupeptin significantly impaired rats' acquisition of this task. Experiment Two assessed rats' performance in a win-stay or a win-shift avoidance task, and it was found that rats in the win-shift group learned the task more efficiently. This win-shift avoidance task was then used in Experiment Three to assess the temporal dependence of leupeptin's behavioral effects by introducing a delay of 1 min, 15 min, or 30 min between the information and choice trials. Leupeptin impaired choice performance at the 30 min delay only. In addition, leupeptin significantly impaired previously-acquired avoidance responding. Because a time-dependent memory deficit was observed, these data are considered to be consistent with the biological model of memory formation advanced by Lynch & Baudry (1984), however no adequate explanation of leupeptin's deleterious effects on previously acquired responding presently exists.
"]},{"key":"dc:title","label":"Title","values":["EFFECTS OF LEUPEPTIN ON AVERSIVELY MOTIVATED SPATIAL MEMORY"]}]}],"canonical_facts":{"dc:creator":["OTTO, TIMOTHY ANDREW"],"dc:description.abstract":["Recent evidence indicates that the activation of a calcium-dependent proteinase, calpain, results in the formation of new glutamate receptors in the hippocampus (Lynch, Halpain, & Baudry, 1982), a brain area commonly thought to play a crucial role in mammalian memory formation. In vitro, this effect is correlated with a long-lasting enhancement of efficacy in synaptic transmission (long-term potentiation, LTP) following brief pulses of electrical stimulation in the hippocampus (Dunwiddie & Lynch, 1979). Because the induction properties of LTP are similar to the behavioral properties of memory, it has been proposed to be the physiological basis of memory (Lynch & Baudry, 1984). If the calcium-dependent activation of calpain is responsible for the induction of LTP and ultimately memory formation, then pharmacologically blocking the calcium-calpain interactions should block those forms of memory dependent on this mechanism.
Three experiments were conducted to assess the effects of leupeptin, a proteinase (calpain) inhibitor on aversively motivated spatial memory in rats. In Experiment One, either leupeptin (8 mg/ml isotonic saline) or isotonic saline was infused continuously into the cerebrospinal fluid, and rats were trained in a one-way avoidance task with one-hour intertrial intervals, three trials per day, for 11 days. Leupeptin significantly impaired rats' acquisition of this task. Experiment Two assessed rats' performance in a win-stay or a win-shift avoidance task, and it was found that rats in the win-shift group learned the task more efficiently. This win-shift avoidance task was then used in Experiment Three to assess the temporal dependence of leupeptin's behavioral effects by introducing a delay of 1 min, 15 min, or 30 min between the information and choice trials. Leupeptin impaired choice performance at the 30 min delay only. In addition, leupeptin significantly impaired previously-acquired avoidance responding. Because a time-dependent memory deficit was observed, these data are considered to be consistent with the biological model of memory formation advanced by Lynch & Baudry (1984), however no adequate explanation of leupeptin's deleterious effects on previously acquired responding presently exists.
"],"dc:identifier":["https://scholars.unh.edu/dissertation/1497"],"dc:subject":["Psychology","Psychobiology"],"dc:title":["EFFECTS OF LEUPEPTIN ON AVERSIVELY MOTIVATED SPATIAL MEMORY"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T05:23:21Z"}