Cytoarchitecture and cortical connections of the anterior insula and adjacent frontal motor fields in the rhesus monkey.

The cytoarchitecture and cortical connections of the ventral motor region are investigated using Nissl, and NeuN staining methods and the fluorescent retrograde tract tracing technique in the rhesus monkey. On the basis of gradual laminar differentiation, it is shown that the ventral motor region stems from the ventral proisocortical area (anterior insula and dorsal Sylvian opercular region). The cytoarchitecture of the ventral motor region is shown to progress in three lines, as we have recently shown for the dorsal motor region. Namely, root (anterior insular and dorsal Sylvian opercular area ProM), belt (ventral premotor cortex) and core (precentral motor cortex) lines. This stepwise architectonic organization is supported by the overall patterns of corticocortical connections. Areas in each line are sequentially interconnected (intralineal connections) and all lines are interconnected (interlinear connections). Moreover, root areas, as well as some of the belt areas of the ventral and dorsal trend are interconnected. The ventral motor region is also connected with the ventral somatosensory areas in a topographic manner. The root and belt areas of ventral motor region are connected with paralimbic, multimodal and prefrontal (outer belt) areas. In contrast, the core area has a comparatively more restricted pattern of corticocortical connections. This architectonic and connectional organization is consistent in part, with the functional organization of the ventral motor region as reported in behavioral and neuroimaging studies which include the mediation of facial expression and emotion, communication, phonic articulation, and language in human.

Cytoarchitecture and cortical connections of the anterior cingulate and adjacent somatomotor fields in the rhesus monkey.

The cytoarchitecture and cortical connections of the anterior cingulate, medial and dorsal premotor, and precentral region are investigated using the Nissl and NeuN staining methods and the fluorescent retrograde tract tracing technique. There is a gradual stepwise laminar change in the cytoarchitectonic organization from the proisocortical anterior cingulate region, through the lower and upper banks of the cingulate sulcus, to the dorsolateral isocortical premotor and precentral motor regions of the frontal lobe. These changes are characterized by a gradational emphasis on the lower stratum layers (V and VI) in the proisocortical cingulate region to the upper stratum layers (II and III) in the premotor and precentral motor region. This is accompanied by a progressive widening of layers III and VI, a poorly delineated border between layers III and V and a sequential increase in the size of layer V neurons culminating in the presence of giant Betz cells in the precentral motor region. The overall patterns of corticocortical connections paralleled the sequential changes in cytoarchitectonic organization. The proisocortical areas have connections with cingulate motor, supplementary motor, premotor and precentral motor areas on the one hand and have widespread connections with the frontal, parietal, temporal and multimodal association cortex and limbic regions on the other. The dorsal premotor areas have connections with the proisocortical areas including cingulate motor areas and supplementary motor area on the one hand, and premotor and precentral motor cortex on the other. Additionally, this region has significant connections with posterior parietal cortex and limited connections with prefrontal, limbic and multimodal regions. The precentral motor cortex also has connections with the proisocortical areas and premotor areas. Its other connections are limited to the somatosensory regions of the parietal lobe. Since the isocortical motor areas on the dorsal convexity mediate voluntary motor function, their close connectional relationship with the cingulate areas form a pivotal limbic-motor interface that could provide critical sources of cognitive, emotional and motivational influence on complex motor function.

Caregiver competence to prevent home injury to the care recipient with dementia.

Home safety is a major concern for persons with a progressive dementia, such as Alzheimer's disease, because much direct care is provided in the home setting. This study used the Home Safety/Injury Model as a frame work to describe the domain of caregiver competence, one of the model's key constructs. Interview data from the perspectives of 17 informants yielded a total of 68 clinical situations that allowed exploration of the scope and dimensions of caregiver competence to prevent accidents in the home. The factors most influential for effective caregiver prevention of home injury were family support, an acceptance and ability to make role changes, teaching and role modeling from professionals, and long-standing values and family traditions. No single factor was sufficient to achieve effective caregiving for making the home safer, but the strength of one or two factors could compensate for the absence of others.

Visual contrast enhances food and liquid intake in advanced Alzheimer's disease.

BACKGROUND & AIMS: Patients with severe Alzheimer's disease (AD) in long-term care have deficient contrast sensitivity and poor food and liquid intake. The present study examined how contrast manipulations affect these intake levels. METHODS: Participants were nine men with advanced AD. Independent variables were meal type (lunch and supper) and condition (baseline, intervention, and post-intervention). Dependent variables were amount of food (grams) and liquid (ounces). Data were collected for 30 days (10 days per condition) for two meals per day. White tableware was used for the baseline and post-intervention conditions, and high-contrast red tableware for the intervention condition. In a follow-up study 1 year later, other contrast conditions were examined (high-contrast blue, low-contrast red and low-contrast blue). RESULTS: Mean percent increase was 25% for food and 84% for liquid for the high-contrast intervention (red) versus baseline (white) condition, with 8 of 9 participants exhibiting increased intake. In the follow-up study, the high-contrast intervention (blue) resulted in significant increases in food and liquid intake; the low-contrast red and low-contrast blue interventions were ineffectual. CONCLUSIONS: Simple environmental manipulations, such as contrast enhancement, can significantly increase food and liquid intake in frail demented patients with AD.

Promoting safer home environments for persons with Alzheimer's disease. The Home Safety/Injury Model.

This article describes a Home Safety/Injury Model derived from Social Cognitive Theory. The model's three components are safety platform, the person with dementia, and risky behaviors. The person with dementia is in the center, located on the safety platform composed of the physical environment and caregiver competence. The interaction between the underlying dementia and indicators of frailty can lead to the person with dementia performing risky behaviors that can overcome the safety platform's resources and lead to an accident or injury, and result in negative consequences. Through education and research, the model guides proactive actions to prevent risky behaviors of individuals with dementia by promoting safer home environments and increased caregiver competence.

Cytoarchitecture and cortical connections of the posterior cingulate and adjacent somatosensory fields in the rhesus monkey.

The cytoarchitecture and connections of the caudal cingulate and medial somatosensory areas were investigated in the rhesus monkey. There is a stepwise laminar differentiation starting from retrosplenial area 30 towards the isocortical regions of the medial parietal cortex. This includes a gradational emphasis on supragranular laminar organization and general reduction of the infragranular neurons as one proceeds from area 30 toward the medial parietal regions, including areas 3, 1, 2, 5, 31, and the supplementary sensory area (SSA). This trend includes a progressive increase in layer IV neurons. Area 23c in the lower bank and transitional somatosensory area (TSA) in the upper bank of the cingulate sulcus appear as nodal points. From area 23c and TSA the architectonic progression can be traced in three directions: one culminates in areas 3a and 3b (core line), the second in areas 1, 2, and 5 (belt line), and the third in areas 31 and SSA (root line). These architectonic gradients are reflected in the connections of these regions. Thus, cingulate areas (30, 23a, and 23b) are connected with area 23c and TSA on the one hand and have widespread connections with parieto-temporal, frontal, and parahippocampal (limbic) regions on the other. Area 23c has connections with areas 30, 23a and b, and TSA as well as with medial somatosensory areas 3, 1, 2, 5, and SSA. Area 23c also has connections with parietotemporal, frontal, and limbic areas similar to areas 30, 23a, and 23b. Area TSA, like area 23c, has connections with areas 3, 1, 2, 5, and SSA. However, it has only limited connections with the parietotemporal and frontal regions and none with the parahippocampal gyrus. Medial area 3 is mainly connected to medial and dorsal sensory areas 3, 1, 2, 5, and SSA and to areas 4 and 6 as well as to supplementary (M2 or area 6m), rostral cingulate (M3 or areas 24c and d), and caudal cingulate (M4 or areas 23c and d) motor cortices. Thus, in parallel with the architectonic gradient of laminar differentiation, there is also a progressive shift in the pattern of corticocortical connections. Cingulate areas have widespread connections with limbic, parietotemporal, and frontal association areas, whereas parietal area 3 has more restricted connections with adjacent somatosensory and motor cortices. TSA is primarily related to the somatosensory-motor areas and has limited connections with the parietotemporal and frontal association cortices.

Facial frequency manipulation normalizes face discrimination in AD.

People with AD have deficient contrast sensitivity and impaired face discrimination. The authors presented photographs of unfamiliar faces of three different sizes to enhance the low, middle, or high facial frequency information (cycles per face). Patients with AD demonstrated normal discrimination of small faces only, indicating that impaired contrast sensitivity at low facial frequencies contributes to their poor face discrimination.

Cortical connections of the frontoparietal opercular areas in the rhesus monkey.

The connections of the frontoparietal opercular areas were studied in rhesus monkeys by using antero- and retrograde tracer techniques. The rostral opercular cortex including the gustatory and proisocortical motor (ProM) areas is connected with precentral areas 3, 1, and 2 as well as with the rostral portion of the opercular area which resembles the second somatosensory type of cortex (area SII) and the ventral portion of area 6. Its distant connections are with the ventral portion of prefrontal areas 46, 11, 12, and 13 as well as with the rostral insula and cingulate motor area (CMAr). The mid opercular region (areas 1 and 2) is connected with pre- and postcentral areas 3, 1, and 2 as well as SII. Additionally, it is connected with the ventral portion of area 6, area 44, area ProM, the gustatory area, and the rostral insula. Its distant connections are with area 4, the ventral portion of area 46, area 7b, and area POa in the intraparietal sulcus (IPS). The rostral parietal opercular region is connected with the postcentral portions of areas 3, 1, and 2; areas 5, 7, and SII; the gustatory area; and the vestibular area. Its other connections are with area 4, area 44, the ventral portion of area 46, area ProM, CMAr, and the supplementary motor area (SMA). The caudal opercular region is connected with the dorsal portion of area 3; areas 2, 5, and 7a; and areas PEa as well as IPd of IPS. It is also connected with area SII, insula, and the superior temporal sulcus. Its distant connections are with area 44; the dorsal portion of area 8 and the ventral portion of area 46; as well as CMAr, SMA, and the supplementary sensory area. This connectivity suggests that the ventral somatosensory areas are involved in sensorimotor activities mainly related to head, neck, and face structures as well as to taste. Additionally, these areas may have a role in frontal (working) and temporal (tactile) memory systems.

Localization of pontine PGO wave generation sites and their anatomical projections in the rat.

A number of experimental and theoretical reports have suggested that the ponto-geniculo-occipital (PGO) wave-generating cells are involved in the generation of rapid eye movement (REM) sleep and REM sleep dependent cognitive functions. No studies to date have examined anatomical projections from PGO-generating cells to those brain structures involved in REM sleep generation and cognitive functions. In the present study, pontine PGO wave-generating sites were mapped by microinjecting carbachol in 74 sites of the rat brainstem. Those microinjections elicited PGO waves only when made in the dorsal part of the nucleus subcoeruleus of the pons. In six rats, the anterograde tracer biotinylated dextran amine (BDA) was microinjected into the physiologically identified cholinoceptive pontine PGO-generating site to identify brain structures receiving efferent projections from those PGO-generating sites. In all cases, small volume injections of BDA in the cholinoceptive pontine PGO-generating sites resulted in anterograde labeling of fibers and terminals in many regions of the brain. The most important output structures of those PGO-generating cells were the occipital cortex, entorhinal cortex, piriform cortex, amygdala, hippocampus, and many other thalamic, hypothalamic, and brainstem nuclei that participate in the generation of REM sleep. These findings provide anatomical evidence for the hypothesis that the PGO-generating cells in the pons could be involved in the generation of REM sleep. Since PGO-generating cells project to the entorhinal cortex, piriform cortex, amygdala, and hippocampus, these PGO-generating cells could also be involved in the modulation of cognitive functions.

Distribution of inhibitory synapses on the somata of pyramidal neurons in cat motor cortex.

The mechanisms by which cortical neurons perform spatial and temporal integration of synaptic inputs are dependent, in large part, on the numbers, types, and distributions of their synapses. To further our understanding of these integrative mechanisms, we examined the distribution of synapses on identified classes of cortical neurons. Pyramidal cells in the cat motor cortex projecting either to the ipsilateral somatosensory cortex or to the spinal cord were labeled by the retrograde transport of horseradish peroxidase. Entire soma of selected corticocortical and corticospinal cells were examined using serial-section electron microscopy. The profiles of these somata and the synapses formed with each of these profiles were reconstructed from each thin section with a computer-aided morphometry system. All somatic synapses were of the symmetrical, presumably inhibitory type. For both cell types, these synapses were not homogeneously distributed over the somatic membrane, but were clustered at several discrete zones. The number and density of synapses on the somata of different corticocortical and corticospinal neurons were not significantly different. However, the density of these synapses was inversely correlated with the size of their postsynaptic somata. We discuss the significance of these findings to the integrative properties of cortical neurons.

Persistent vegetative state in Alzheimer disease. Does it exist?

OBJECTIVE: To determine if the published criteria for diagnosis of the persistent vegetative state could be applied to patients suffering from Alzheimer disease. DESIGN AND METHODS: Eighty-eight institutionalized patients with a diagnosis of possible or probable Alzheimer disease were evaluated for the presence of persistent vegetative state. Initial screening excluded patients who were able to do any of the following: feed themselves, respond to command, walk, or maintain continence of bowel and bladder. A sample of 12 of 28 patients unable to perform any of these functions was examined independently by 3 of us. RESULTS: During the first examination, 2 patients were diagnosed as being in a vegetative state by 2 of us and 3 additional patients by 1 of us. One of us did not diagnose any patient as being in a vegetative state. A second evaluation of the same patients was performed 2 months later, after holding a consensus meeting to standardize the evaluation procedure. During the second evaluation, the vegetative state was diagnosed in 6 patients but only by 1 of us. CONCLUSION: The diagnostic disagreement between the neurologists indicate that Alzheimer disease may only rarely progress to the persistent vegetative state.

Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo.

Nitric oxide may be a key mediator of excitotoxic neuronal injury in the central nervous system. We examined the effects of the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) on excitotoxic striatal lesions. 7-NI significantly attenuated lesions produced by intrastriatal injections of NMDA, but not kainic acid or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) 7-NI attenuated secondary striatal excitotoxic lesions produced by the succinate dehydrogenase inhibitor malonate, and the protection was reversed by L-arginine but not by D-arginine, 7-NI produced nearly complete protection against striatal lesions produced by systemic administration of 3-nitropropionic acid (3-NP), another succinate dehydrogenase inhibitor, 7-NI protected against malonate induced decreases in ATP, and increases in lactate, as assessed by 1H magnetic resonance spectroscopy. 7-NI had no effects on spontaneous electrophysiologic activity in the striatum in vivo, suggesting that its effects were not mediated by an interaction with excitatory amino acid receptors. 7-NI attenuated increases in hydroxyl radical, 8-hydroxy-2-deoxyguanosine and 3-nitrotyrosine generation in vivo, which may be a consequence of peroxynitrite formation. The present results implicate neuronal nitric oxide generation in the pathogenesis of both direct and secondary excitotoxic neuronal injury in vivo. As such they suggest that neuronal nitric oxide synthase inhibitors may be useful in the treatment of neurologic diseases in which excitotoxic mechanisms play a role.

Involvement of free radicals in excitotoxicity in vivo.

Recent evidence has linked excitotoxicity with the generation of free radicals. We examined whether free radical spin traps can attenuate excitotoxic lesions in vivo. Pretreatment with N-tert-butyl-alpha-(2-sulfophenyl)-nitrone (S-PBN) significantly attenuated striatal excitotoxic lesions in rats produced by N-methyl-D-aspartate (NMDA), kainic acid, and alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA). In a similar manner, striatal lesions produced by 1-methyl-4-phenylpyridinium (MPP+), malonate, and 3-acetylpyridine were significantly attenuated by either S-PBN or alpha-phenyl-N-tert-butylnitrone (PBN) treatment. Administration of S-PBN in combination with the NMDA antagonist MK-801 produced additive effects against malonate and 3-acetylpyridine toxicity. Malonate injections resulted in increased production of hydroxyl free radicals (.OH) as assessed by the conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid (DHBA). This increase was significantly attenuated by S-PBN, consistent with a free radical scavenging effect. S-PBN had no effects on malonate-induced ATP depletions and had no significant effect on spontaneous striatal electrophysiologic activity. These results provide the first direct in vivo evidence for the involvement of free radicals in excitotoxicity and suggest that antioxidants may be useful in treating neurologic illnesses in which excitotoxic mechanisms have been implicated.

Movement disorder following excitotoxin lesions in primates.

We previously reported on the histologic and neurochemical features of quinolinic acid lesions in primates which produce many of the characteristic features of Huntington's disease (HD). We now report on the effects of apomorphine in generating a movement disorder in four of these animals. Animals were tested with saline or apomorphine both before and after the lesions. All animals showed few spontaneous abnormal movements after lesioning, but showed marked dyskinetic movements following apomorphine administration. These results show that excitotoxin lesions in primates can produce an apomorphine-inducible movement disorder which closely resembles that of HD.

Excitotoxin lesions in primates as a model for Huntington's disease: histopathologic and neurochemical characterization.

Excitotoxin lesions induced by quinolinic acid (QA) were made unilaterally in the caudate nucleus and putamen of 12 rhesus monkeys. Both acute (2-3 weeks) and chronic (4-6 months) effects were evaluated. Excitotoxin striatal lesions were characterized by a central zone of intense astrogliosis and marked neuronal depletion, which was surrounded by a transition zone in which there was partial neuronal sparing throughout the entire lesioned side. Immunocytochemical and enzyme histochemical markers for both large and medium-sized aspiny- and spiny-striatal neurons clearly demonstrated a selective pattern of neuronal vulnerability to the excitotoxic effects of QA within lesioned striata. Medium-sized spiny neurons containing calbindin Dk28, enkephalin, and substance P were disproportionately lost, while aspiny neuronal subpopulations containing NADPH diaphorase (NADPH-d) and choline acetyltransferase activity (ChAT) were relatively spared. Combined labeling by NADPH-d enzyme histochemistry and Nissl staining, as well as NADPH-d histochemistry and calbindin Dk28 immunocytochemistry, demonstrated significant increases in the ratio of aspiny to spiny neurons within the lesioned striata. Neurochemical measurements confirmed a loss of GABA and substance P-like immunoreactivity yet no significant depletion of somatostatin-like immunoreactivity, neuropeptide Y-like immunoreactivity, or ChAT were seen. The striatal patch-matrix pattern persisted, as demonstrated by acetylcholinesterase activity. The pattern was altered, however, in the chronic animals, such that the matrix zone was significantly reduced, while the total area of patches remained within normal limits. Ultrastructural analysis confirmed axon sparing lesions with neuronal loss and astrogliosis. Pretreatment of 3 monkeys with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, blocked striatal QA neurotoxicity. The present results provide an experimental primate model which closely resembles the neuropathologic and neurochemical features of Huntington's disease. These findings further strengthen the possibility that an NMDA receptor-mediated excitotoxic process plays a role in the pathogenesis of this disorder.

Golgi, histochemical, and immunocytochemical analyses of the neurons of auditory-related cortices of the rhesus monkey.

Morphological characteristics of the neurons of the auditory cortical areas of the rhesus monkey were investigated using Golgi and horseradish peroxidase methods. Neurons of the auditory cortices can be segregated into two categories, spinous and nonspinous, which can be further subclassified according to their dendritic arrays. The spinous neurons include pyramidal, "star pyramid," multipolar, and bipolar cells. As in other cortices, pyramidal cells are found in layers II-VI and appear to be the most numerous of all cortical neurons. The "star pyramids" have radially oriented dendrites with a less prominent apical shaft and are found mainly in the middle cortical layers. The spinous multipolar neurons are also found in the middle cortical layers and have their dendrites radially arrayed but have no apical dendrite. The spinous bipolar cells, found in the infragranular layers, occur most frequently in the lateral auditory association cortex. The nonspinous neurons include neurogliaform, multipolar, bitufted, and bipolar cells and are found in all cortical layers. The neurogliaform cells are the smallest of all neurons and have radially arrayed, recurving dendrites. The nonspinous multipolar cells also have radially arrayed dendrites but vary in size from being confined to one cortical layer to extending across four laminae. The bitufted neurons are subclassified into three groups: neurons whose primary dendrites arise radially from their somata, those whose dendrites arise from two poles of their somata, and those that have a single primary dendrite arising from one pole and multiple dendrites from another pole of their somata. The nonspinous bipolar cells also have several variants but usually have dendrites arising from two poles of the somata. The chemical characteristics of the auditory neurons were investigated using histochemical and immunocytochemical methods. Peptidergic neurons, i.e., cholecystokinin-, vasoactive intestinal polypeptide-, somatostatin-, and substance P-reactive neurons are found in the various subregions of the auditory cortices and are distributed differentially in the cortical laminae. These neurons are of the nonpyramidal type. Gamma aminobutyric acid-reactive neurons are also nonpyramidal cells and they are found in all cortical layers. Their numbers varied among the cortical laminae in the different auditory regions.(ABSTRACT TRUNCATED AT 400 WORDS)

Neurons of the lateral entorhinal cortex of the rhesus monkey: a Golgi, histochemical, and immunocytochemical characterization.

This study identifies the neuronal types of the rhesus monkey lateral entorhinal cortex (LEC) and discusses the importance of these data in the context of the connectional patterns of the LEC and the possible role of these cells in neurodegenerative diseases. These neuronal types were characterized with the aid of Golgi impregnation techniques. These characterizations were based upon their spine densities, dendritic arrays, and, where possible, axonal arborizations. The cells could be segregated into only spinous and sparsely spinous types. The most numerous spinous types were pyramidal neurons. Other spinous types included multipolar, vertical bipolar and bitufted, and vertical tripolar neurons. The sparsely spinous neuronal types consisted of multipolar, horizontal bipolar and bitufted, and neurogliaform cells. These cells were further classified with the aid of histochemical stains and immunocytochemical markers. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry stained multipolar, bipolar, and bitufted neurons. Stain for cytochrome oxidase (CO) was found in pyramidal and nonpyramidal cell types. Immunocytochemical techniques revealed several nonpyramidal neurons that contain somatostatin (Som) or substance P (SP). This study complements previous analyses of the neuronal components described in the LEC and adds further information about the distribution of selected neurochemicals within this cortex.

Thalamocortical synapses with identified neurons in monkey primary auditory cortex: a combined Golgi/EM and GABA/peptide immunocytochemistry study.

The objective of this study was to identify neurons in layer IV of the monkey primary auditory cortex (area KA) that are postsynaptic to thalamocortical axon terminals. Thalamocortical axon terminals were labeled by lesion-induced degeneration; neurons postsynaptic to these afferents were labeled by the Golgi/EM method followed by postembedding immunocytochemistry. Five of the six non-pyramidal neurons examined received synapses from thalamocortical axon terminals. All of these cells were immunoreactive for gamma-aminobutyric acid (GABA). One of the cells stained also with an antiserum to somatostatin, and another for cholecystokinin. None of the cells examined were immunoreactive to substance P, and in no instance were two different peptides co-localized within the same GABA-positive neuron.

Connectional analysis of the ipsilateral and contralateral afferent neurons of the superior temporal region in the rhesus monkey.

The interhemispheric and ipsilateral afferents of the superior temporal region (STR) were investigated with the aid of fluorescent retrograde tracers (Diamidino Yellow and Fast Blue). Different tracers were injected in selected cortical areas of the STR of each hemisphere of four rhesus monkeys. The results show that the interhemispheric afferents originate not only from the homotopic but also from heterotopic areas. The heterotopic areas giving rise to interhemispheric projections correspond to cortical areas of the origin of the ipsilateral projections. Although there is considerable overlap of labeled neurons of both afferent systems, only occasional double-labeled neurons are found. Whereas the laminar patterns of ipsilateral neurons of origin vary considerably, the interhemispheric projection neurons are located mainly in cortical layer III. This study provides additional information about the ipsilateral connectional organization of the superior temporal region. That is, the primary auditory area receives projections not only from adjacent lateral and medial cortical regions but also from adjoining rostral and caudal cortical regions. Thus, the highly differentiated primary auditory cortical area receives strong projections from the surrounding less-differentiated cortical regions. This connectional pattern is discussed from the perspective of the growth ring concept of cortical development.

The identification of thalamocortical axon terminals in barrels of mouse Sml cortex using immunohistochemistry of anterogradely transported lectin (Phaseolus vulgaris-leucoagglutinin).

The anterograde transport and immunohistochemical demonstration of the lectin, Phaseolus vulgaris-leucoagglutinin (PHA-L) has been used to label thalamocortical axon terminals in barrels of mouse SmI cortex. The reaction product is visible with both the light and electron microscopes so that the distribution of axons and the types of synapses they form can be determined.