ABSTRACT
Retrograde amnesia following disruptions of hippocampal function is often temporally graded, with recent memories being more impaired. Evidence supports the existence of one or more neocortical long-term memory storage/retrieval site(s). Neurotoxic lesions of the medial prefrontal cortex (mPFC) or the dorsal hippocampus (DH) were made 1 day or 200 days following trace fear conditioning. Recently encoded trace fear memories were most disrupted by DH lesions, while remotely encoded trace and contextual memories were most disrupted by mPFC lesions. These data strongly support the consolidation theory of hippocampus function and implicate the mPFC as a site of long-term memory storage/retrieval.
Subject(s)
Fear , Hippocampus/physiopathology , Memory Disorders/physiopathology , Nerve Net/physiopathology , Prefrontal Cortex/physiopathology , Amnesia, Retrograde/physiopathology , Animals , Freezing Reaction, Cataleptic , Hippocampus/surgery , Male , Mental Recall/physiology , Prefrontal Cortex/surgery , Rats , Rats, Long-Evans , Time FactorsABSTRACT
The hippocampus is important for the formation of spatial, contextual, and episodic memories. For instance, lesions of the dorsal hippocampus (DH) produce demonstrable deficits in contextual fear conditioning. By contrast, it is generally agreed that the DH is not important for conditioning to a discrete cue (such as a tone or light) that is paired with footshock in a temporally contiguous fashion (delay conditioning). There are, however, some reports of hippocampus involvement in delay conditioning. The present series of experiments was designed to assess the conditions under which the hippocampus-dependent component of delay fear conditioning performance may be revealed. Here, we manipulated the number of conditioning trials and the intensity of the footshock in order to vary the strength of conditioning. The results indicate that the DH contributes to freezing performance to a delay conditioned tone when the conditioning parameters are relatively weak (few trials or low footshock intensity), but not when strong parameters are used. The results are discussed in terms of two parallel memory systems: a direct tone-footshock association that is independent of the hippocampus and a hippocampus-dependent memory for the conditioning session.
Subject(s)
Conditioning, Psychological/physiology , Fear/physiology , Hippocampus/physiology , Memory/physiology , Reflex, Startle/physiology , Acoustic Stimulation , Animals , Behavior, Animal/physiology , Catheterization , Denervation , Electroshock , Excitatory Amino Acid Agonists/toxicity , Hippocampus/pathology , Male , N-Methylaspartate/toxicity , Neurotoxins/pharmacology , Rats , Rats, Long-Evans , Videotape RecordingABSTRACT
Brain atrophy measured by MRI is an important correlate with clinical disability and disease duration in multiple sclerosis (MS). Unfortunately, neuropathologic mechanisms which lead to this grey matter atrophy remain unknown. The objective of this study was to determine whether brain atrophy occurs in the mouse model, experimental autoimmune encephalomyelitis (EAE). Postmortem high-resolution T2-weighted magnetic resonance microscopy (MRM) images from 32 mouse brains (21 EAE and 11 control) were collected. A minimum deformation atlas was constructed and a deformable atlas approach was used to quantify volumetric changes in neuroanatomical structures. A significant decrease in the mean cerebellar cortex volume in mice with late EAE (48-56 days after disease induction) as compared to normal strain, gender, and age-matched controls was observed. There was a direct correlation between cerebellar cortical atrophy and disease duration. At an early time point in disease, 15 days after disease induction, cerebellar white matter lesions were detected by both histology and MRM. These data demonstrate that myelin-specific autoimmune responses can lead to grey matter atrophy in an otherwise normal CNS. The model described herein can now be used to investigate neuropathologic mechanisms that lead to the development of gray matter atrophy in this setting.
Subject(s)
Cerebellar Cortex/pathology , Encephalomyelitis, Autoimmune, Experimental/complications , Encephalomyelitis, Autoimmune, Experimental/pathology , Animals , Atrophy , Brain Mapping , Female , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Mice , Mice, Inbred C57BL , Myelin Proteins/immunology , Nonlinear DynamicsSubject(s)
Acetylcholine/physiology , Avoidance Learning/physiology , Conditioning, Psychological/physiology , Fear/physiology , Receptors, Muscarinic/physiology , Receptors, Nicotinic/physiology , Synaptic Transmission , Animals , Conditioning, Classical/physiology , Humans , Prosencephalon/physiology , Receptors, Muscarinic/genetics , Receptors, Nicotinic/geneticsABSTRACT
Like other accounts of conditioned inhibition, behavior systems predicts (and Experiment 1 shows) that during summation and retardation tests, presentation of a negative conditioned stimulus (a CS-) created by discriminative Pavlovian food conditioning will interfere with a focal search response, such as nosing in the feeder. Unlike most other views, behavior systems predicts (and Experiment 2 shows) that the same CS- can potentiate a general search response, like attending to a moving artificial prey stimulus. Contacting the prey stimulus in extinction increased over baseline when a CS- but not a CS Novel preceded it. Experiment 3 showed this effect was not due to unconditioned qualities of the CS-. It appears that the effects of a discriminative CS- depend on the interaction of the training contingency with search modes related to the unconditioned stimulus (US), their perceptual-motor repertoires and environmental support, and the choice of response measure.
