Ibotenic acid lesions of the medial septum retard delay eyeblink conditioning in rabbits (Oryctolagus cuniculus)

S. Berry and R. Thompson (1979) reported that electrolytic lesions of the medial septum significantly retard eyeblink conditioning. However, these electrolytic lesions were nonselective and may have also damaged the subcortical inputs to the hippocampus via the fimbria–fornix. In the present study, the medial septum was selectively lesioned with ibotenic acid in rabbits (Oryctolagus cuniculus), whose performance in a delay eyeblink conditioning paradigm was compared with that of intact controls, sham-operated controls, and intact controls given a systemic injection of scopolamine. Rabbits with selective medial septal lesions and rabbits receiving systemic scopolamine were significantly slower to condition than were intact and sham-lesioned rabbits. This finding demonstrates that the selective removal of the medial septum retards delay eyeblink conditioning in a manner similar to the disruption seen after systemic administration of scopolamine. One interesting feature of work from classical eyeblink conditioning is the finding that, although a hippocampal lesion does not affect delay eyeblink conditioning (Schmaltz & Theios, 1972), a disruption of hippocampal activity greatly retards delay eyeblink conditioning (Berry & Thompson, 1979; Solomon, Solomon, Vander Shaaf, & Perry, 1983). Classical eyeblink conditioning is a simple associative learning paradigm in which a neutral stimulus (the conditioned stimulus [CS], usually a tone or light) is paired with a response-evoking stimulus (the unconditioned stimulus [US], usually a corneal airpuff or periorbital eye shock). Initially, the tone elicits no behavioral response, whereas the airpuff elicits a reflexive eyeblink. By repeatedly pairing the tone and airpuff, the tone alone comes to elicit an eyeblink response (the conditioned response [CR]).

[1]  E. Brazhnik,et al.  Acetylcholine, theta-rhythm and activity of hippocampal neurons in the rabbit—III. Cortical input , 1993, Neuroscience.

[2]  JOHN W. Moore,et al.  Central cholinergic blockade by scopolamine and habituation, classical conditioning, and latent inhibition of the rabbit’s nictitating membrane response , 1976 .

[3]  J. Theios,et al.  Acquisition and extinction of a classically conditioned response in hippocampectomized rabbits (Oryctolagus cuniculus). , 1972, Journal of comparative and physiological psychology.

[4]  W. Seifert Neurobiology of the hippocampus , 1983 .

[5]  S. D. Berry,et al.  Medial septal lesions retard classical conditioning of the nicitating membrane response in rabbits. , 1979, Science.

[6]  P. Solomon,et al.  The septohippocampal cholinergic system and classical conditioning of the rabbit's nictitating membrane response. , 1981, Journal of comparative and physiological psychology.

[7]  S. D. Berry,et al.  Scopolamine disruption of septo-hippocampal activity and classical conditioning. , 1989, Behavioral neuroscience.

[8]  D. A. Powell Peripheral and central muscarinic cholinergic blockade: Effects on Pavlovian conditioning , 1979 .

[9]  C. Geula,et al.  Complete and selective cholinergic denervation of rat neocortex and hippocampus but not amygdala by an immunotoxin against the p75 NGF receptor , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  P. Solomon,et al.  Latent inhibition and stimulus generalization of the classically conditioned nictitating membrane response in rabbits (Oryctolagus cuniculus) following dorsal hippocampal ablation. , 1975, Journal of comparative and physiological psychology.

[11]  I. Gormezano,et al.  Effects of scopolamine and methylscopolamine on classical conditioning of the rabbit nictitating membrane response. , 1983, The Journal of pharmacology and experimental therapeutics.

[12]  O. Vinogradova,et al.  Acetylcholine, theta-rhythm and activity of hippocampal neurons in the rabbit—I. Spontaneous activity , 1993, Neuroscience.

[13]  I. Urban,et al.  A stereotaxic atlas of the New Zealand rabbit's brain , 1972 .

[14]  M. Hasselmo Neuromodulation and cortical function: modeling the physiological basis of behavior , 1995, Behavioural Brain Research.

[15]  O. Vinogradova,et al.  Acetylcholine, theta-rhythm and activity of hippocampal neurons in the rabbit—IV. Sensory stimulation , 1993, Neuroscience.

[16]  M. Hasselmo,et al.  A Computational Model of Cholinergic Disruption of Septohippocampal Activity in Classical Eyeblink Conditioning , 1996, Neurobiology of Learning and Memory.

[17]  M. M. Patterson,et al.  Fimbrial lesions and sensory preconditioning. , 1984, Behavioral neuroscience.

[18]  D. Powell,et al.  Divergencies in Pavlovian conditioned heart rate and eyeblink responses produced by hippocampectomy in the rabbit (Oryctolagus cuniculus). , 1980, Behavioral and neural biology.

[19]  L. Jarrard On the use of ibotenic acid to lesion selectively different components of the hippocampal formation , 1989, Journal of Neuroscience Methods.

[20]  R. Wiley,et al.  Immunolesioning: selective destruction of neurons using immunotoxin to rat NGF receptor , 1991, Brain Research.

[21]  G. Buzsáki,et al.  Phase relations of hippocampal projection cells and interneurons to theta activity in the anesthetized rat , 1983, Brain Research.

[22]  Intracerebral scopolamine administration attenuates Pavlovian heart rate conditioning in the rabbit , 1985, The Pavlovian journal of biological science.

[23]  T. Freund,et al.  GABA-containing neurons in the septum control inhibitory interneurons in the hippocampus , 1988, Nature.

[24]  J. B. Ranck,et al.  Hippocampal theta rhythm and the firing of neurons in walking and urethane anesthetized rats , 2004, Experimental Brain Research.

[25]  G. Buzsáki Two-stage model of memory trace formation: A role for “noisy” brain states , 1989, Neuroscience.

[26]  P. Solomon,et al.  Altered activity in the hippocampus is more detrimental to classical conditioning than removing the structure. , 1983, Science.

[27]  John F. Disterhoft,et al.  A system for quantitative analysis of associative learning. Part 1. Hardware interfaces with cross-species applications , 1994, Journal of Neuroscience Methods.

[28]  M. Gluck,et al.  Dissociating entorhinal and hippocampal involvement in latent inhibition , 2000 .

[29]  W. B. Orr,et al.  Hippocampectomy selectively disrupts discrimination reversal conditioning of the rabbit nictitating membrane response , 1983, Behavioural Brain Research.

[30]  I. Gormezano,et al.  Relationship between heterosynaptic reflex facilitation and acquisition of the nictitating membrane response in control and scopolamine- injected rabbits , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.