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N A Buchwald

Publications and source records attributed to N A Buchwald.

At least 37 records · Page 2Linked to original sources

Dye-coupling in the neostriatum of the rat: II. Decreased coupling between neurons during development.

Physiological and morphological evidence for coupling between neostriatal neurons was obtained from the developing rat. Intracellular injections of Lucifer Yellow-CH (LY) were made in rat neostriatal slices to study dye transfer (coupling) between neurons. The incidence of interneuronal coupling was 70% in early postnatal (P) periods and declined gradually to 10% in the adult. The number of neurons filled by a single intracellular injection also declined with age. LY injection into single neurons commonly marked aggregates of 4 to 6 cells in neonates. Single injections never produced more than one coupled pair in P20 or older rats. Neurons in which fast prepotentials (FPPs) could be evoked were consistently found to be dye-coupled. FPPs were resistant to collision with action potentials generated by intracellular current injection. When chemical synaptic transmission was blocked Mn2+, short-latency depolarizations (SLDs) could be evoked by extracellular stimulation. The SLDs were distinguished from chemical synaptic potentials by their "all or none" nature and by their insensitivity to changes in membrane potential. No SLDs were observed in adult neurons. FPPs and SLDs may be indicators of electronic transmission between coupled cells. The high incidence of coupling early in development might reflect intercellular communication that contributes to the differentiation and growth of neostriatal neurons.

Action Potentials↗

GABAergic basal forebrain neurons project to the neocortex: the localization of glutamic acid decarboxylase and choline acetyltransferase in feline corticopetal neurons.

Our objective was to determine whether GABAergic and cholinergic basal forebrain neurons project to the neocortex. The retrograde connectivity marker wheat germ agglutinin lectin-bound horseradish peroxidase was injected into the neocortex of adult cats. Histo- and immunohistochemical methods were combined to label sequentially connectivity and transmitter markers (glutamic acid decarboxylase; choline acetyltransferase) in forebrain neurons. The labels of each marker were identified by correlative light and electron microscopy. Two principal types of doubly labeled neurons were demonstrated. The connectivity marker was colocalized with glutamic acid decarboxylase or choline acetyltransferase. The neurons were located in the basal forebrain. Their ultrastructural, cellular, and regional organization supported 2 conclusions. (1) GABAergic basal forebrain neurons project to the neocortex. This is important new morphological evidence for the origin of inhibitory neocortical afferents from a subcortical brain site. (2) The GABAergic and cholinergic basal forebrain neurons projecting to the neocortex exhibit remarkable structural similarities. The transmitter diversity of these intertwined neocortical afferents may be significant for the pathology and treatment of human neurological disorders such as Alzheimer's disease.

Animals↗

Ultrastructural alterations in caudate nucleus in aged cats.

These studies provide information on the changes in the ultrastructure in the caudate nucleus of aged cats. The major finding was that there was a decrease in the density of synapses in caudate neuropil. This decrease occurred in animals after 3 years of age and remained relatively constant in older animals. In conjunction with this change a population of unusually long synapses also occurred. These larger synaptic appositions were associated with enlarged spine heads. The caudate also showed a number of qualitative ultrastructural alterations. Many neurons contained accumulations of lipofuscin or lipopigment granules in aged animals. These inclusions occurred in both soma and dendrites of neurons and all types of glial cells. A unique configuration of collapsed agranular cisterns also was observed in aged animals. The present results indicate that decreases in synaptic density may be one morphological event underlying functional alterations observed in caudate neurons in aged cats.

Aging↗

Physiological and morphological characterization of striatal neurons transplanted into the striatum of adult rats.

Physiological and morphological properties of transplanted striatal neurons (TSNs) were examined in an in vitro slice preparation. Fetal striatal tissue (E13-14) was implanted as a dissociated cellular suspension into the striatum of adult rats. Intracellular records were obtained from TSNs 2-6 weeks after transplantation. TSNs exhibited biophysical, morphological, and synaptic properties characteristic of normal striatal neurons, despite the disruption involved in processing of the fetal tissue. Differences were observed, however, between the TSNs and host striatal neurons. TSNs consistently had higher input resistance values than host striatal neurons as determined by neuronal responses to intracellular current injection. Stimulation of adjacent host striatum elicited both excitatory and inhibitory postsynaptic potentials in TSNs. By contrast, the same stimuli elicited only excitatory responses in host striatal neurons. Morphologically, TSNs resembled host medium-size spiny neurons as demonstrated by intracellular injection of lucifer yellow. However, the complexity of dendritic branching and the density of spines on the dendrites were less than that observed for host striatal neurons. It was concluded that during the posttransplantation period studied, TSNs possess neuronal properties expected of developmentally immature striatal neurons.

Action Potentials↗

Aging reduces somatosensory responsiveness of caudate neurons in the awake cat.

Neuronal activity was recorded in 7 awake cats (3 animals 11-15 years and 4 animals 1-3 years of age) to determine if the ability of caudate neurons to process facial somatosensory information was impaired in aged animals. Proportionately fewer neurons responded to somatosensory stimuli and facial receptive fields were larger in the aged cats. In addition, proportionately fewer caudate neurons responded to cortical activation, there were fewer excitatory responses and spontaneous firing decreasing in aged cats. These results provide additional evidence that excitability of caudate neurons is reduced in aged cats.

Action Potentials↗

Neurophysiological alterations in caudate neurons in aged cats.

These neurophysiological studies provide information on the alterations in functional capacity of neurons in the aging caudate nucleus (Cd) of the cat. The major finding is that there is a marked loss of excitation in the Cd during the aging process. This loss is most apparent in animals 11-14 years of age but is demonstrable in animals 6-7 years of age. Extracellular recording techniques were used to test the ability of Cd neurons to respond to activation of two of their major inputs, the precruciate cortex (CX) and the substantia nigra (SN). Types of responses that were evoked in both 1-3- and 11-14-year groups were similar and consisted of excitation, excitation followed by inhibition of action potentials or inhibition alone without preceding excitation. The frequency of occurrence of these responses was altered in the aged animals when either input was stimulated. In 1-3-year-old cats CX stimulation evoked initially excitatory responses in 75% of the cells tested while in 11-14-year-old cats excitatory responses occurred in 62% of the cells. When the SN was stimulated the decrease in initial excitation was greater (69% in 1-3- vs 35% in 11-14-year groups). In all aged animals but not in 1-3-year-old cats stimulation thresholds were higher (39-79%) for evoking excitatory responses than for evoking inhibitory responses. In order to assess synaptic security, the ability of Cd neurons to respond to iterative stimulation was determined. Distributions of the minimum interval necessary to evoke two excitatory responses were constructed. There was a marked increase in the proportion of longer intervals in the aged animals indicating that the synaptic response was less secure. There was a tendency for more of the responses in aged animals to have shorter latencies. This result was probably due to loss of less secure longer latency responses that are mediated via multisynaptic pathways. These findings indicate that there are functional changes in a population of Cd neurons in aged cats that impair their ability to process information.

Action Potentials↗

The morphogenesis of glutamic acid decarboxylase in the neostriatum of the cat: neuronal and ultrastructural localization.

Correlative light and electron microscopic immunohistochemical methods were adapted for a descriptive analysis of the normal time course and pattern of expression and intraneuronal localization of the enzyme glutamic acid decarboxylase (GAD) in the neostriatum (Ns) of fetal, postnatal and adult cats. The differentiation of this synthesizing enzyme demonstrated the establishment of gamma-aminobutyric acid (GABA) transmitter identity in these neurons and their connections. The structural modifications of these GABAergic profiles revealed the morphogenesis of important inhibitory synaptic inputs in the Ns. The expression of GAD began during late fetal development and proceeded in a diagonal gradient from the first-formed ventrolateral putamen to the last-formed dorsomedial caudate nucleus. The frequency of GAD-positive elements increased with age particularly during the early postnatal period. After the initial expression of GAD, 3 interrelated processes contributed to its differentiation: (1) enzyme accumulation; (2) enzyme association with membranous organelles and (3) progressive elaboration of neuronal infrastructure. Synaptogenesis was both coincident and subsequent to GAD differentiation. Two principal types of GABAergic structures, cell bodies and axonal 'terminals', were evident from the initiation of GAD expression. The GABAergic cell bodies were polymorphic by and after the day of birth and consisted of ubiquitous medium sized cells (often having somatic and/or dendritic spines) and rare large sized cells (apparently aspiny and confined to a limited region of the Ns). The GABAergic axonal terminals changed from growth cone and prototerminal forms to mature bouton en passage and bouton terminaux forms establishing axosomatic and axodendritic contracts, having symmetric synaptic specializations and providing inputs to both medium- and large-sized GABAergic target neurons.

Aging↗

The GABAergic striatonigral neurons of the cat: demonstration by double peroxidase labeling.

GABAergic striatonigral neurons were demonstrated in the adult cat by the specific double peroxidase labeling of a transmitter marker with an agranular appearance (GAD, the synthetic enzyme of GABA) and a connectivity marker with a granular appearance (WGA-HRP). Each marker was associated with different organelles confined to the perikaryal cytoplasm of neurons. GABAergic striatonigral neurons were of medium size, high frequency and wide location in the rostral caudate nucleus and putamen based on correlative light and electron microscopic identification. These cells had somatic and/or proximal dendritic spines and folded nuclear envelopes in some cases. They received GABAergic axosomatic and axodendritic inputs with symmetric synaptic specializations. They were also contacted by axosomatic, axodendritic and axospinous terminals with asymmetric synaptic specializations. These results indicate that the GABAergic striatonigral neurons are, for the most part, medium spiny cells that also emit intrastriatal axonal collaterals. Their intra- and extrastriatal axons mediate inhibitory postsynaptic influences on their targets. Their degeneration might contribute to the GABAergic deficits found in the basal ganglia in Huntington's disease.

Animals↗

Physiological and morphological analyses of ventral anterior and ventral lateral thalamic neurons in the cat.

Intracellular recordings were made from ventral anterior and ventral lateral (VA-VL) thalamic neurons in the cat. VA-VL neurons were tested for responsiveness to activation of cortical, pallidal and cerebellar afferents, and were identified morphologically by intracellular injection of HRP. Orthodromic activation of cortical and pallidal afferents produced primarily an initial inhibition (due in part to oligosynaptic circuitry) while activation of cerebellar afferents produced an initial excitation in the majority of neurons tested. Antidromic activation of thalamocortical relay neurons was observed in 32% of the neurons tested. Neurons showing short latency responses to activation of globus pallidus-entopeduncular nucleus and cerebellar peduncle were concentrated in the medical and ventral portions of the VA-VL complex, respectively. Neurons showing short latency responses to activation of the neocortex were located throughout the entire extent of the VA-VL complex. Only 3% of the neurons tested showed short-latency convergence of cortical, pallidal and cerebellar afferents. In contrast, 53% of neurons tested showed long latency triple convergence. Eight VA-VL neurons were stained intracellularly with HRP. Based on dendritic morphology, the labeled neurons were separated into two types: a stellate type with dendrites that spread radially from the soma, and a fusiform type with dendrites that were oriented mainly parallel to the long axis of the soma. Both types of neuron were aspiny although the dendrites of the stellate cells exhibited short appendages.

Animals↗

Basal forebrain neurons have axon collaterals that project to widely divergent cortical areas in the cat.

Basal forebrain neurons with axon collaterals that project to widely divergent cortical areas were identified using retrograde transport of two labels. A proportion of neurons in the basal forebrain have axon collaterals that project to both anterior (precruciate gyrus) and posterior (marginal and suprasylvian gyri) cortical areas or to medial (precruciate gyrus) and lateral (ectosylvian and anterior suprasylvian gyri) cortical areas. These branched fibers originate from cells located predominantly in the basal nucleus of Meynert. The existence of such neurons suggests that individual basal forebrain cells are capable of influencing widespread neocortical zones in the cat.

Afferent Pathways↗

Neurons of origin of striatonigral axons in the cat: connectivity and Golgi markers of somatodendritic architecture.

We identified adult cat striatonigral neurons and characterized their somatodendritic architecture by single- and double-labeling with connectivity and Golgi markers. Light and electron microscopic observations demonstrated two important structural variations among striatofugal neurons. First, striatonigral axons originate from multiple types of neurons. The principal striatonigral neurons are frequent throughout the caudate nucleus and putamen, have medium spherical or ovoidal cell bodies and form spine-laden distal dendrites. The 'accessory' striatonigral neurons are sparse in limited regions of the caudate nucleus and putamen, have large fusiform cell bodies and lack spinous processes. Second, the medium spiny striatonigral neurons exhibit a range of anatomical specializations. In some cases, these cells have folded nuclear envelopes. Some of these neurons have somatic and/or proximal dendritic as well as distal dendritic spines. We conclude that adult cat striatofugal neurons are morphologically heterogeneous in terms of regional locations, somatodendritic architecture and ultrastructure. These anatomical specializations may affect the origin and processing of synaptic inputs to the neostriatum to provide functionally different routes of neurotransmission through the basal ganglia.

Animals↗

Branched projections of cat sensorimotor cortex: multiple retrograde labeling via commissural corticocortical, decussated corticostriatal and undecussated corticostriatal axons.

The common origins and interrelationships of commissural corticocortical and descending corticostriatal projections were assessed by multiple retrograde labeling of neurons in the precruciate sensorimotor cortex of the cat. The major finding was that some of these neurons had axons that branched at least twice to send collaterals to contralateral cortical sites and bilateral subcortical sites in the caudate nucleus. Regardless of their collateralization, these axons originated mainly from pyramidal neurons of small-medium size located in cortical laminae III-V. A considerable component of the corticocortical and corticostriatal inputs derived from the same neurons. These fibers subserve both intra- and interhemispheric linkages of the sensorimotor cortex with itself and the basal ganglia.

Animals↗

The entopeduncular nucleus: Golgi morphometrics of serially reconstructed neurons in adult cats.

Computer-assisted morphometrics were used to characterize mature somatodendritic architecture in Golgi-stained neurons of the entopeduncular nucleus (EN) of the adult cat. Only one form of adult EN neuron was apparent and characterized by common features including: relatively large conical somata, long aspiny and moderately branched dendrites and discoid to spherical dendritic fields oriented randomly within the EN. These results indicate that feline EN neurons have some properties in common with large neurons of the primate medial pallidal segment.

Animals↗

Axonal branching of basal forebrain projections to the neocortex: a double-labeling study in the cat.

Double-labeling of basal forebrain neurons by retrograde axonal transport demonstrates divergent collateralization among undecussated axonal projections to the neocortex. These branched fibers originate from a considerable complement of large polymorphic cell bodies located mainly in the basal nucleus of Meynert. They terminate in multiple neocortical sites including the precruciate, postcruciate and/or cingulate gyri. This extensive intra- and intergyral axonal branching indicates that neurons in the basal forebrain of the cat have extensive axonal fields innervating adjacent neocortical gyri.

Animals↗

Postnatal development of identified medium-sized caudate spiny neurons in the cat.

The morphology of intracellularly recorded neurons in the cat caudate nucleus (Cd) was studied during postnatal development. After intracellular recording of evoked responses in these neurons, horseradish peroxidase (HRP) was injected iontophoretically through the recording micropipette. Fifty-eight Cd neurons in cats ranging from 6 days of age through adulthood were identified morphologically. All of the recovered Cd cells were medium-sized spiny neurons. The basic somatodendritic morphology of these neurons was evident in the youngest kittens. The most striking morphological change was the postnatal formation of an extensive local axonal collateral plexus. The development of these local axonal collaterals was also quantified with computer assistance in medium-sized Cd spiny neurons selected from silver-impregnated material. This analysis showed that the major development of the branches of this local plexus occurred between birth and 3-4 months of postnatal age. Data from both the HRP-filled and silver-stained axons indicated that the postnatal growth of the local axonal collaterals of the medium spiny cells was associated with the elaboration and increasing prevalence of evoked inhibitory postsynaptic potentials in Cd neurons.

Age Factors↗

Postnatal differentiation and growth of cat entopeduncular neurons. A transient spiny period associated with branch elongation.

Qualitative and computer-assisted analyses were performed on Golgi-impregnated neurons which were serially reconstructed in 3 dimensions. Analysis of the temporal pattern of growth indicated that the initial outgrowth, formation of the adult number of dendrites and virtually all dendritic branching occurred in the prenatal period. About 40% of the total growth of the dendrites occurred in the postnatal period. Maturation was completed by 90-120 days. Analyses of the mode of dendritic growth and of the morphological changes associated with growth revealed two significant findings. First, the outward expansion of the dendritic tree was not due to the addition of new branches but resulted from the elongation of terminal and non-terminal branches. Thus, growth occurred between branch points as well as on terminal portions of dendrites. Second, a transient population of spines was found during the period of postnatal growth. These spines may play an integral role in synaptogenesis and dendritic branch elongation. We suggest that developing afferent fibers initially contact spines. As spines retract, axon terminals are brought to the shaft of the dendrites. Further, the dendrites elongated because membrane associated with spines is incorporated into the shafts of dendrites. Striopallidal projections and other afferents may provide an important trophic influence for the normal dendritic differentiation of pallidal neurons by inducing the elaboration or retraction of spines.

Aging↗

Branched projections of pallidal and peripallidal neurons to neocortex and neostriatum: a double-labeling study in the cat.

Double-labeling of basal forebrain neurons by retrograde axonal transport of different markers demonstrated afferents shared by the neocortex and neostriatum. A considerable double-labeled complement of neurons located in the globus pallidus (lateral pallidal segment) and the adjacent interdigitating basal nucleus of Meynert (peripallidal region) had branched axonal collaterals projecting to the precruciate, cingulate and prorean gyri as well as to the head of the caudate nucleus.

Animals↗

Behavioral effects of D-amphetamine in developing cats.

The development of the behavioral effects of amphetamine was assessed in kittens of 1-53 days of age. Amphetamine-induced increases in locomotion occurred when animals were beyond 35 days of age. Stereotypic behavior was induced at all ages tested but the predominant type of stereotypy was age-related. From 1 to 14 days amphetamine induced licking. Pendular head movements occurred when animals were under 35 days. At 14 days of age darting, a response consisting of rapid pacing and turning began to occur. Tracking, a series of horizontal and vertical head movements also began to occur after 14 days. The adult response of vertical and horizontal head movements became most prominent after 35 days.

Age Factors↗