Damage to the perirhinal cortex exacerbates memory impairment following lesions to the hippocampal formation.

Recent work has been directed at identifying the critical components of the medial temporal lobe that, when damaged, produce severe memory impairment. The H+A+ lesion includes the hippocampal formation, the amygdala, and the adjacent entorhinal, parahippocampal, and perirhinal cortices. A more restricted medial temporal lobe lesion that includes the hippocampal formation and parahippocampal cortex (the H+ lesion) produces less severe memory impairment. Previous work demonstrated that extending the H+ lesion forward to include the amygdala did not exacerbate the impairment. Here, we tested the hypothesis that extending the H+ lesion forward to include the perirhinal cortex (the H++ lesion), but sparing the amygdala, should produce a more severe memory impairment and one that would approximate the level of memory impairment associated with the H+A+ lesion. Monkeys with the H++ lesion were severely impaired on two of three amnesia-sensitive tasks (delayed nonmatching to sample and delayed retention of object discrimination). On the third amnesia-sensitive task (concurrent discrimination learning), two of the monkeys in the H++ group obtained poorer scores than all seven normal monkeys, although the overall group comparison was not significant. The memory impairment following H++ damage was more severe overall than the impairment associated with the H+ lesion and approached the level of impairment associated with the H+A+ lesions. Quantitative measurement of damage in each anatomical component of the lesion indicated that the perirhinal cortex was the only brain region that was more extensively damaged in the H++ group than in the H+ group. These findings emphasize the importance of the perirhinal cortex in the anatomy of the medial temporal lobe memory system.

Enduring memory impairment in monkeys after ischemic damage to the hippocampus.

Patient RB became amnesic following an episode of global ischemia that resulted in a bilateral lesion of the CA1 field of the hippocampus. This finding suggested that damage restricted to the hippocampus is sufficient to produce clinically significant memory impairment. To evaluate further the effect of ischemic brain damage on memory, we have developed an animal model of cerebral ischemia in the monkey. Monkeys were subjected to 15 min of reversible ischemia, using a noninvasive technique involving carotid occlusion and pharmacologically induced hypotension. These monkeys sustained significant loss of pyramidal cells in the CA1 and CA2 fields of the hippocampus, as well as loss of somatostatin-immunoreactive cells in the hilar region of the dentate gyrus. Cell loss occurred bilaterally throughout the rostrocaudal extent of the hippocampus but was greater in the caudal portion. Except for patchy loss of cerebellar Purkinje cells, significant damage was not detected in areas outside the hippocampus, including adjacent cortical regions, that is, entorhinal, perirhinal, and parahippocampal cortex, and other regions that have been implicated in memory function. On behavioral tests, the ischemic monkeys exhibited significant and enduring memory impairment. On the delayed nonmatching to sample task, the ischemic monkeys were as impaired as monkeys with lesions of the hippocampal formation and adjacent parahippocampal cortex (the H+ lesion). On two other memory tasks, the ischemic monkeys were less impaired than monkeys with the H+ lesion. In neuropathological evaluations, it has always been difficult to rule out the possibility that significant areas of neuronal dysfunction have gone undetected. The finding that ischemic lesions produced overall less memory impairment than H+ lesions indicates that the ischemic monkeys (and by extension, patient RB) are unlikely to have widespread neuronal dysfunction affecting memory that was undetected by histological examination. These results provide additional evidence that the hippocampus is a focal site of pathological change in cerebral ischemia, and that damage limited to the hippocampus is sufficient to impair memory.

Stereotaxic lesions of the hippocampus in monkeys: determination of surgical coordinates and analysis of lesions using magnetic resonance imaging.

A technique is described for producing accurate stereotaxic lesions of the hippocampus in monkeys. This technique overcomes the problem that the size and shape of the brain can vary considerably from monkey to monkey. Magnetic resonance imaging (MRI) is used to create an individual brain atlas for each monkey. The atlas is then used to derive coordinates for making stereotaxic radio frequency lesions of the hippocampus. There are two key features of this procedure. First, a specially-designed, acrylic, stereotaxic headholder was constructed that could be used safely with the MR magnet. Second, small glass beads, anchored to the skull of the monkey, served as common landmarks from which lesion coordinates were determined in the MR images and then again in neurosurgery. MRI techniques are also described for determining the extent of tissue damage postoperatively. This technique could also prove useful in other areas of neuroscience research that depend on accurate stereotaxic placement of electrodes (e.g., electrophysiological studies and neuroanatomic tracing studies).

Independence of memory functions and emotional behavior: separate contributions of the hippocampal formation and the amygdala.

Structures and connections in the medial temporal lobe of humans and nonhuman primates have long been recognized as important for normal memory and emotional behavior. The present study investigated memory and emotional behavior in normal monkeys and six groups of monkeys with lesions of the medial temporal lobe. Two groups had damage to the hippocampal formation (or adjacent perirhinal and parahippocampal cortex) but not the amygdaloid complex; two groups had either partial or complete damage to the amygdaloid complex but not the hippocampal formation; and two groups had damage to both the hippocampal formation and the amygdaloid complex. Memory was evaluated with three tasks sensitive to human amnesia: (1) delayed nonmatching to sample; (2) retention of object discriminations; and (3) concurrent discrimination learning. Emotional behavior was assessed by measuring the responsiveness of monkeys to 12 different stimulus situations. Damage to the hippocampal formation or anatomically related cortex impaired memory but did not affect emotional behavior. Partial or complete damage to the amygdaloid complex affected emotional behavior but not memory. These findings show that memory impairment and abnormal emotional behavior are anatomically dissociable and independent effects of damage to the medial temporal lobe.

Synaptic plasticity in the hypoglossal nucleus of female canaries: structural correlates of season, hemisphere, and testosterone treatment.

The caudal portion of the hypoglossal nucleus (nXIIts) contains the motor neurons that control the syrinx in songbirds. In canaries, song occurs seasonally, is principally produced by males, and appears to be produced predominantly by muscles on the left side of the syrinx. The present study measures the effect of seasonal change and manipulation of testosterone levels on synapse number and morphology in nXIIts in adult female canaries. We find that synapse density is lower in testosterone-treated birds than in control birds and lower in fall than in spring. The number of vesicles per presynaptic profile increases in the spring as a result of a general increase in this measure in all synapses. The number of vesicles per presynaptic profile also increases with testosterone treatment, primarily due to an increase in the proportion of synapses associated with unusually high vesicle counts. Together, these changes suggest that large reserves of neurotransmitter may be necessary to sustain singing. Several ultrastructural differences between hemispheres are found. Postsynaptic thickenings are longer, and postsynaptic processes are larger on the left side than on the right side. In the spring, there are more vesicles per synapse on the left than on the right, but this lateralization is reversed in the fall. Thus, lateralization of song production is associated with lateral asymmetries in synapse morphology. These hemispheric differences are relatively small, like those seen at the light microscope level, encouraging further consideration of peripheral as well as CNS sources of functional lateralization. The seasonal and testosterone-induced changes in synapse number and morphology may be components of the periodic reorganization of canary vocalization.

Song-related brain regions in the red-winged blackbird are affected by sex and season but not repertoire size.

Previous work in songbirds has delimited a neural system responsible for song production and control. Earlier studies have suggested that functional capacity in the song system may be related to the mass of the system in an animal's brain, and that adult plasticity in this neural system may be related to adult capacity for behavioral modification. We now test these hypotheses in adult red-winged blackbirds (Agelaius phoeniceus), a species in which song is produced primarily by males, new song types are added to the male's repertoire in adulthood, and there are substantial differences among males in song complexity. We find that the song system in males is much larger than in females. Song system nuclei become smaller in both sexes as the animals experience shorter days. We do not find any association between repertoire size and size of any of the song system structures examined. Thus, although sex differences in song may be related to differences between sexes in the mass of song system structures, individual differences in song do not appear to be directly related to mass within males. Seasonal change in song system structures in male redwings is consistent with there being a relation between adult plasticity in anatomy and in behavior; the large seasonal change in these structures in females suggests large seasonal changes in the function of these nuclei.