Although the role of acetylcholine in processing stimuli in the cerebral cortex is becoming defined, the impact of cholinergic activity on the character of cortical maps remadns unclear. In the somatosensory cortex, topographic maps appear capable of lifelong modifications in response to alterations in the periphery. One factor proposed to influence this adaptational ability is the presence of acetylcholine in the cortex. The studies presented here, using the 2-deoxyglucose technique, demonstrate that the unilateral removal of a digit in cats, followed by stimulation of an adjacent digit, produces a pattern of metabolic activity in the somatosensory cortex that is dramatically expanded when compared with the opposite (normal) hemisphere. In contrast, experiments in which the somatosensory cortex was depleted of acetylcholine and the animal received a similar amputation led not to patterns of expanded metabolic activity, but rather to reductions in the evoked metabolic distribution. These studies implicate acetylcholine in normal map formation and in the maintenance of the capacity of cortical maps to adapt to changes in the periphery.Several lines of evidence suggest that the cholinergic projection from the basal forebrain plays an important role in cortical physiology and plasticity. For example, in 1986, Bear and Singer (1) demonstrated that depletion of cortical acetylcholine (ACh) following lesions of the basal forebrain disrupts ocular dominance plasticity in kitten area 17. Interestingly, this effect required the concurrent depletion of cortical norepinephrine. Cortical ACh depletion has also been shown to cause a reduction in the cortical response to sensory stimulation, measured both electrophysiologically (2) and metabolically (3, 4). For example, Sato et al. (2) found that lesions of the basal forebrain, which depleted the visual cortex of ACh, led to neuronal responses in visual cortex that were sluggish and depressed. Previous studies in cat somatosensory cortex found that ACh depletion by basal forebrain lesions, or by the pharmacologic antagonism of ACh through topical applications of atropine, caused the stimulus-evoked metabolic pattern to be reduced in dimension and intensity in the hemisphere ipsilateral to the depletion or application of atropine (3). On the other hand, iontophoretic application of exogenous ACh can augment the responses to peripheral stimulation in visual, somatosensory, and auditory cortex (5-11). In these sensory cortical regions, the pairing of ACh with appropriate stimuli usually enhances cortical responses. In some cases, the augmentation substantially outlasts presentation of the stimulus, causing a long-lasting potentiation of neuronal responsivity (11)(12)(13)(14).In the somatosensory cortex, topographic maps of the body surface appear capable of remodeling and demonstrating plastic changes throughout adulthood. Studies that evaluate the cortical response to various peripheral manipulations in adults show dramatic rearrangements of cortical topographic maps ...

Although long-term memory is thought to require a cellular program of gene expression and increased protein synthesis, the identity of proteins critical for associative memory is largely unknown. We used RNA fingerprinting to identify candidate memory-related genes (MRGs), which were up-regulated in the hippocampus of water maze-trained rats, a brain area that is critically involved in spatial learning. Two of the original 10 candidate genes implicated by RNA fingerprinting, the rat homolog of the ryanodine receptor type-2 and glutamate dehydrogenase (EC 1.4.1.3), were further investigated by Northern blot analysis, reverse transcription-PCR, and in situ hybridization and confirmed as MRGs with distinct temporal and regional expression. Successive RNA screening as illustrated here may help to reveal a spectrum of MRGs as they appear in distinct domains of memory storage.Identifying the mechanisms responsible for memory formation and consolidation has long been a goal of behavioral neuroscience. Many experiments over the past few decades have demonstrated that inhibitors of transcription or translation interfere with long-term memory formation, indicating the requirement of de novo gene expression (1-4). Despite the importance of this finding, little is known about the identity and specificity of the required proteins. Changes in early inducible genes, for example, are known to occur not only during learning and memory, but also during a broad range of behaviors, including motor activity and sensory discrimination (5-10). Changes in the expression of late effector genes, such as those encoding BiP and calreticulin, have been described during long-term sensitization in Aplysia but not in associative memory (11,12). To our knowledge, no changes in late effector genes have been previously demonstrated during associative memory.To identify memory-related genes (MRGs) we have used a new and sensitive approach, RNA fingerprinting by arbitrarily primed PCR (13,14), to compare gene expression in control swimming rats with water maze-trained rats. The Morris water maze is a learning paradigm in which a rodent learns to locate a submerged island in a large pool by creating a spatial map using extra-pool cues (15)(16)(17). This learning ability represents a complex faculty involving input from different senses including visual, olfactory, auditory, and somatosensory information (18)(19)(20). The hippocampus has been shown to be a brain locus for spatial memory (21). Pyramidal cells in the rat hippocampus discharge selectively at specific locations of a spatial environment (22, 23) and maintain their receptive field when the relevant cues are removed (24) or when the light is turned off (25). Lesions of the hippocampus result in impaired acquisition of tasks that depend on spatial strategies (26-28) and spatial memory impairment parallels the magnitude of dorsal hippocampal lesions (29). MATERIALS AND METHODSWater Maze Learning. Male Wistar rats, 60-90 days old (200-300 g) were housed individually in plastic cages wi...

The fine structure of spinal and trigeminal projections to the parabrachial area (PB) of the rat was studied using either the anterograde transport of a lectin-peroxidase conjugate or the degeneration technique. Two morphologically different types of terminals were observed. Most labeled terminals contained round vesicles (R type) and formed asymmetrical synapses, usually with large dendrites. Others contained pleomorphic vesicles (P type) and usually made symmetrical contacts with large or medium-size dendrites. A double-labeling strategy was used, combining the retrograde labeling of PB neurons with lectin-peroxidase conjugate from the amygdala and the identification of degenerating terminals after lesions of spinal or trigeminal pathways. These experiments demonstrated that spinal and trigeminal terminals contact PB neurons that project to the central nucleus of the amygdala. The role of this spino(trigemino)-ponto-amygdalian pathway is discussed in relation to some aspects of pain.