Cholinergic and noncholinergic septal neurons modulate strategy selection in spatial learning

Rats solving a simple spatial discrimination task in a plus maze initially employ a place‐learning strategy, then switch to a motor response strategy. The hippocampus is required for the use of a place‐learning strategy in this task. Rats with 192 IgG‐saporin lesions of the medial septum/vertical limb of the diagonal band (MS/VDB), that selectively removed cholinergic neurons projecting to the hippocampus, were significantly facilitated in acquisition of the spatial discrimination, and switched from place to response strategies just as control rats did. Rats with ibotenic acid lesions of the MS/VDB, that produced cell loss in the MS/VDB but little damage to cholinergic neurons, were significantly impaired in acquiring the spatial discrimination and did not reliably employ either a place or response strategy at any point in training. This suggests that the MS/VDB modulates hippocampal involvement in place learning, but that cholinergic MS/VDB neurons are neither necessary nor sufficient for using a place strategy to solve a spatial discrimination.

[1]  K. Pang,et al.  Interactions between 192-IgG saporin and intraseptal cholinergic and GABAergic drugs: role of cholinergic medial septal neurons in spatial working memory. , 1999, Behavioral neuroscience.

[2]  F. Fonnum,et al.  Radiochemical micro assays for the determination of choline acetyltransferase and acetylcholinesterase activities. , 1969, The Biochemical journal.

[3]  R. Kesner,et al.  Involvement of the Prelimbic–Infralimbic Areas of the Rodent Prefrontal Cortex in Behavioral Flexibility for Place and Response Learning , 1999, The Journal of Neuroscience.

[4]  S. Heckers,et al.  Differential effects on spatial navigation of immunotoxin-induced cholinergic lesions of the medial septal area and nucleus basalis magnocellularis , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  M. Gallagher,et al.  Hippocampal lesions disrupt decrements but not increments in conditioned stimulus processing , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  J. O'Keefe,et al.  The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. , 1971, Brain research.

[7]  A. Grace,et al.  Compensatory responses to nigrostriatal bundle injury. Studies with 6-hydroxydopamine in an animal model of parkinsonism. , 1989, Molecular and chemical neuropathology.

[8]  M. Baxter,et al.  Selective immunolesions of hippocampal cholinergic input fail to impair spatial working memory , 1997, Hippocampus.

[9]  R. Gaykema,et al.  Cortical projection patterns of the medial septum‐diagonal band complex , 1990, The Journal of comparative neurology.

[10]  M. Sarter,et al.  Dissociation between the attentional functions mediated via basal forebrain cholinergic and GABAergic neurons , 2001, Neuroscience.

[11]  G. M. Peterson,et al.  Morphological evidence for a substance P projection from medial septum to hippocampus , 1992, Peptides.

[12]  M. M. Glasier,et al.  Intraseptal injections of 192 IgG saporin produce deficits for strategy selection in spatial-memory tasks , 1998, Behavioural Brain Research.

[13]  D. Olton,et al.  Lesions in nucleus basalis magnocellularis and medial septal area of rats produce qualitatively similar memory impairments , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  L. Wilkinson,et al.  Behavioural, histochemical and biochemical consequences of selective immunolesions in discrete regions of the basal forebrain cholinergic system , 1994, Neuroscience.

[15]  M. Gallagher,et al.  Blocking can occur without losses in attention in rats with selective removal of hippocampal cholinergic input. , 1999, Behavioral neuroscience.

[16]  J. D. McGaugh,et al.  Inactivation of Hippocampus or Caudate Nucleus with Lidocaine Differentially Affects Expression of Place and Response Learning , 1996, Neurobiology of Learning and Memory.

[17]  L. Swanson The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[18]  Tamás F. Freund,et al.  GABAergic septohippocampal neurons contain parvalbumin , 1989, Brain Research.

[19]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[20]  P. Holland,et al.  Disruption of Decrements in Conditioned Stimulus Processing by Selective Removal of Hippocampal Cholinergic Input , 1997, The Journal of Neuroscience.

[21]  P. Dutar,et al.  Potentiation of glutamatergic EPSPs in rat CA1 hippocampal neurons after selective cholinergic denervation by 192 IgG‐saporin , 1997, Synapse.

[22]  P. Dutar,et al.  Alteration of NMDA receptor‐mediated synaptic responses in CA1 area of the aged rat hippocampus: Contribution of GABAergic and cholinergic deficits , 1998, Hippocampus.

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

[24]  R. Morris,et al.  Place navigation in rats is impaired by lesions of medial septum and diagonal band but not nucleus basalis magnocellularis , 1988, Behavioural Brain Research.

[25]  C. Barnes Spatial learning and memory processes: the search for their neurobiological mechanisms in the rat , 1988, Trends in Neurosciences.

[26]  L. Thal,et al.  Time course of cholinergic and monoaminergic changes in rat brain after immunolesioning with 192 IgG-saporin , 1994, Neuroscience Letters.

[27]  J. E. Kelsey,et al.  Medial septal lesions disrupt spatial mapping ability in rats. , 1988, Behavioral neuroscience.

[28]  H. Blodgett,et al.  Place versus response learning in the simple T-maze. , 1947, Journal of experimental psychology.

[29]  M. Packard Glutamate infused posttraining into the hippocampus or caudate-putamen differentially strengthens place and response learning. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[30]  J. Mills,et al.  Sexually dimorphic responses to neonatal basal forebrain lesions in mice: I. Behavior and neurochemistry. , 1998, Journal of neurobiology.

[31]  K. Pang,et al.  GABAergic septohippocampal neurons are not necessary for spatial memory , 2001, Hippocampus.

[32]  S. L. Mobley,et al.  The Effects of Selective Cholinergic Basal Forebrain Lesions and Aging upon Expectancy in the Rat , 1997, Neurobiology of Learning and Memory.

[33]  M. Baxter,et al.  Cholinergic basal forebrain is critical for social transmission of food preferences , 2000, Hippocampus.

[34]  A. Chiba,et al.  A re-examination of the role of basal forebrain cholinergic neurons in spatial working memory , 1998, Neuropharmacology.

[35]  F. Restle Discrimination of cues in mazes: a resolution of the place-vs.-response question. , 1957, Psychological review.

[36]  M. Gallagher,et al.  Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats. , 1995, Behavioral neuroscience.