NEUROwords. 8. Plasticity and neuroplasticity.
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Animals↗
Biomedical subjects
E G Jones
Publications and source records attributed to E G Jones.
Cortical and subcortical contributions to activity-dependent plasticity in primate somatosensory cortex.
After manipulations of the periphery that reduce or enhance input to the somatosensory cortex, affected parts of the body representation will contract or expand, often over many millimeters. Various mechanisms, including divergence of preexisting connections, expression of latent synapses, and sprouting of new synapses, have been proposed to explain such phenomena, which probably underlie altered sensory experiences associated with limb amputation and peripheral nerve injury in humans. Putative cortical mechanisms have received the greatest emphasis but there is increasing evidence for substantial reorganization in subcortical structures, including the brainstem and thalamus, that may be of sufficient extent to account for or play a large part in representational plasticity in somatosensory cortex. Recent studies show that divergence of ascending connections is considerable and sufficient to ensure that small alterations in map topography at brainstem and thalamic levels will be amplified in the projection to the cortex. In the long term, slow, deafferentation-dependent transneuronal atrophy at brainstem, thalamic, and even cortical levels are operational in promoting reorganizational changes, and the extent to which surviving connections can maintain a map is a key to understanding differences between central and peripheral deafferentation.
Afferent Pathways↗
Plasticity and neuroplasticity.
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History, 19th Century↗
Predominance of corticothalamic synaptic inputs to thalamic reticular nucleus neurons in the rat.
Quantitative electron microscopy was used to examine the relative contributions of different types of synapses to the circuitry of the thalamic reticular nucleus (RTN) in the rat. Single RTN cells were injected with Lucifer Yellow (LY) in fixed brain slices and examined after photoconversion; corticothalamic axons and terminals were labeled by anterograde transport of Phaseolus vulgaris-leucoagglutinin (PHA-L); and gamma-aminobutyric acid (GABA)ergic terminals were labeled by postembedding immunocytochemistry. Three types of synapses, made by morphologically distinguishable small terminals (ST), large terminals (LT), and GABAergic terminals, were distributed on all portions of the dendritic trees of injected RTN cells. ST and LT terminals formed asymmetrical, presumed excitatory, synaptic contacts. On proximal dendrites, approximately 50% of the synapses were ST, 30-40% were LT, and 10-25% were GABAergic. On distal dendrites, 60-65% were ST, 20% were LT, and 15% were GABAergic. PHA-L labeling showed that labeled corticothalamic terminals and ST terminals have identical morphological features and the same distribution patterns on RTN dendrites, indicating that the majority of excitatory afferents to RTN neurons are derived from the cerebral cortex. The LT terminals found in smaller numbers are probably derived from collateral axons of thalamocortical relay cells. GABAergic terminals formed by LY-labeled, intra-RTN axon collaterals were relatively few in number, and no dendrodendritic synapses were observed.
Animals↗
Development of metabotropic glutamate receptors from trigeminal nuclei to barrel cortex in postnatal mouse.
Expression patterns of group I (mGluR1alpha and mGluR5) and group II (mGluR2/3) metabotropic glutamate receptor subtypes were examined immunocytochemically in the trigeminal system of mice during the first 3 weeks of postnatal development, when somatotopic whisker representations are sequentially established from brainstem through thalamus to cerebral cortex. Immunostaining for all three epitopes formed whisker-related patterns in the trigeminal nuclei from postnatal day (P) 0, in the ventral posterior thalamic nucleus from P2, and in the posteromedial barrel subfield of somatosensory cortex (SI) from P4. The appearance of whisker-related patterns was preceded by increased levels of immunostaining of the neuropil, which subsequently declined from the trigeminal nuclei upward. In SI, mGluR1alpha-positive neurons were observed in all cortical layers from P2. mGluR5 was localized in neurons, glial cells, and neuropil from P2. mGluR2/3 immunostaining was distributed only in the neuropil at all ages. The three receptor subtypes showed moderate to high expression in deep layer V throughout development. Transient expression peaked in the hollows of layer IV barrels from P4 to P9, and then fell off as expression increased in supragranular layers from P14 to P21. The deep aspect of the cortical subplate (layer VIb) showed dense mGluR5 and less dense mGluR1alpha immunostaining throughout development. Up-regulation of expression of group I and II mGluRs is correlated with the growth and refinement of connectivity and the establishment of somatotopic patterns in the three main relay stations of the trigeminal system. This finding suggests roles for mGluRs in the early processing of sensory information and in developmental plasticity.
Animals↗
Laminar and cellular distribution of AMPA, kainate, and NMDA receptor subunits in monkey sensory-motor cortex.
In situ hybridization histochemistry and immunocytochemistry were used to examine lamina- and cell-specific expression of glutamate receptor (GluR) mRNAs and polypeptide subunits in motor and somatosensory cortex of macaque monkeys. Radioactive complementary RNA (cRNA) probes were prepared from cDNAs specific for alpha-amino-3-hydroxy-5-methylisoxozolepropionate (AMPA)/kainate (GluR1-GluR4), kainate (GluR5-GluR7), and N-methyl-D-aspartate (NMDA; NR1, NR2A-NR2D) receptor subunits. AMPA/kainate and NR1, NR2A, and NR2B receptor transcripts show higher expression than other transcripts. All transcripts show lamina-specific patterns of distribution. GluR2 and GluR4 mRNAs show higher expression than do GluR1 and GluR3 mRNAs. GluR6 transcript expression is higher than that of GluR5 and GluR7. NR1 mRNA expression is much higher than that of NR2 mRNAs. NR2C subunit expression is very low except for a very distinct band of high expression in layer IV of area 3b. Immunocytochemistry, using subunit-specific antisera and double labeling for calbindin, parvalbumin, or alpha type II Ca2+/calmodulin-dependent protein kinase (CaMKII-alpha), allowed identification of cell types expressing different subunit genes. GluR1 and GluR5/6/7 immunoreactivity is found in both pyramidal cells and gamma-amino butyric acid (GABA) cells; GluR2/3 immunoreactivity is preferentially found in pyramidal cells, whereas GluR4 immunoreactivity is largely restricted to GABA cells; NMDA receptor subunit immunoreactivity is far greater in excitatory cells than in GABA cells. The density of expression of AMPA/kainate, kainate, and NMDA receptor subunit mRNAs differed within and across the architectonic fields of sensory-motor cortex. This finding and the lamina- and cell-specific patterns of expression suggest assembly of functional receptors from different arrangements of available subunits in specific neuronal populations.
Animals↗
Assessing the decade of the brain.
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Brain↗
Synchronized paroxysmal activity in the developing thalamocortical network mediated by corticothalamic projections and "silent" synapses.
In mouse thalamocortical slices in vitro, the potassium channel blocker 4-AP and GABAA receptor antagonist bicuculline together induced spontaneous prolonged depolarizations in layer VI neurons from postnatal day 2 (P2), in ventroposterior nucleus neurons (VP) from P7, and in reticular nucleus neurons (RTN) from P8. Dual whole-cell recordings revealed that prolonged bursts were synchronized in layer VI, VP, and RTN. Bursts were present in cortex isolated from thalamus, but not in thalamus isolated from cortex, indicating that bursts originated in cortex and propagated to thalamus. Prolonged bursts were synchronized in layer VI when vertical cuts extended from pia mater through layers IV or V, but were no longer synchronized when cuts extended through layer VI and white matter. In voltage-clamp recordings before P10, burst conductance of all three neuronal populations was dominated by the NMDA receptor-mediated conductance, and therefore synapses were "silent". In cortex and RTN, after P10, bursts were associated with strong AMPA/kainate receptor-mediated conductances, and synapses had become "functional"; silent synapses persisted in a large proportion of VP cells after P10. Before P9, the NMDA receptor antagonist APV or the non-NMDA receptor antagonist CNQX blocked the prolonged bursts. After P9, CNQX continued to block the prolonged bursts, but APV merely shortened their duration. Thus, NMDA receptor-based silent synapses are essential for paroxysmal corticothalamic activity during early postnatal development, and connections between layer VI neurons are sufficient for horizontal cortical synchronization.
4-Aminopyridine↗
Temporal modulation of GABA(A) receptor subunit gene expression in developing monkey cerebral cortex.
In situ hybridization histochemistry was used to examine the expression of 10 GABA(A) receptor messenger RNAs corresponding to the alpha1-alpha5, beta1-beta3, gamma1 and gamma2 subunits in primary somatosensory and visual areas of macaque monkey cerebral cortex from embryonic day (E) 125 to postnatal day (P) 125. Results were compared with expression patterns in adults. In the sensorimotor cortex at E125, overall levels of all subunit transcripts were low. At E137, there was a major lamina-specific increase in all subunit messenger RNAs except gamma1. For alpha1, alpha2, alpha4, beta2, beta3 and gamma2 subunit transcripts, this increase was highest in areas 3a and 3b, particularly in layers III/IV and VI. Postnatally, there were significant decreases in all transcripts. Alpha1, alpha5, beta2 and gamma2 subunit transcripts, while still at significantly lower levels than at E137, remained expressed at levels higher than other transcripts. Unlike in rodents, there was no obvious "switch" in the major subunits expressed in fetal and adult cortex, alpha1, alpha5, beta2 and gamma2 remaining highest throughout. In area 17, the most prominently expressed subunits at earliest ages were alpha2, alpha5, beta1, beta2, beta3 and gamma2, especially in layers II/III and VI. At E150, expression for alpha2, alpha3, beta1 and beta3 subunit transcripts in these layers decreased, but levels for alpha1, alpha4, alpha5, beta2, gamma1 and gamma2 transcripts increased, particularly within layer IV. The increase at E150 was particularly marked for alpha5 transcripts, which were expressed at levels more than four times those of other transcripts. Alpha1, beta2 and gamma2 remain highest into aduthood. Fetal area 17 displayed lamina-specific patterns of expression not found in adult animals. In particular, alpha3 messenger RNAs were present in layer IVA and gamma1 transcripts were present in layer IVC at E150, despite a lack of expression in these layers in the adult. These data demonstrate increased expression of GABA(A) receptors during the period of establishment of thalamocortical and intracortical connections, and a temporal regulation that may be associated with the period of developmental plasticity.
Aging↗
hKCa3/KCNN3 potassium channel gene: association of longer CAG repeats with schizophrenia in Israeli Ashkenazi Jews, expression in human tissues and localization to chromosome 1q21.
We demonstrate a significant association between longer CAG repeats in the hKCa3/KCNN3 calcium-activated potassium channel gene and schizophrenia in Israeli Ashkenazi Jews. We genotyped alleles from 84 Israeli Jewish patients with schizophrenia and from 102 matched controls. The overall allele frequency distribution is significantly different in patients vs controls (P = 0.00017, Wilcoxon Rank Sum test), with patients showing greater lengths of the CAG repeat. Northern blots reveal substantial levels of approximately 9 kb and approximately 13 kb hKCa3/KCNN3transcripts in brain, striated muscle, spleen and lymph nodes. Within the brain, hKCa3/KCNN3transcripts are most abundantly expressed in the substantia nigra, lesser amounts are detected in the basal ganglia, amygdala, hippocampus and subthalamic nuclei, while little is seen in the cerebral cortex, cerebellum and thalamus. In situ hybridization reveals abundant hKCa3/KCNN3 message localized within the substantia nigra and ventral tegmental area, and along the distributions of dopaminergic neurons from these regions into the nigrostriatal and mesolimbic pathways. FISH analysis shows that hKCa3/KCNN3 is located on chromosome 1q21.
Base Sequence↗
Neurochemical gradients along monkey sensory cortical pathways: calbindin-immunoreactive pyramidal neurons in layers II and III.
We examined the distribution of neurons containing immunoreactivity for three calcium-binding proteins, calbindin, parvalbumin and calretinin, as well as nonphosphorylated neurofilament protein, in cortical areas along the ventral and dorsal cortical visual pathways, and in ventrally-directed somatosensory and auditory cortical pathways. Calbindin-immunoreactive pyramidal neurons showed the most prominent regional differences. They were largely restricted to layers II and III and their number monotonically increased from the primary sensory areas to the anteroventral areas along the ventral visual pathway and along the ventrally-directed somatosensory and auditory pathways. The number of calbindin-immunoreactive pyramidal neurons in layers II and III also increased along the dorsal visual pathway, but the number in the last recognized stage of the dorsal visual pathway (area 7a) was significantly smaller than that at the corresponding stage in the ventral visual pathway (TE). The number of calbindin-immunoreactive pyramidal neurons was highest in layers II and III of areas 35/36, TG, and TF/TH, which represent terminal cortical regions of the pathways. These results show neurochemical differences between cortical areas located at early and late stages along serial corticocortical pathways, as well as confirming differences between pyramidal neurons in the supragranular and infragranular layers.
Animals↗
Golgi, Cajal and the Neuron Doctrine.
Camillo Golgi and Santiago Ramon y Cajal shared the Nobel Prize in 1906 for their work on the histology of the nerve cell, but both held diametrically opposed views about the Neuron Doctrine which emphasizes the structural, functional and developmental singularity of the nerve cell. Golgi's reticularist views remained entrenched and his work on the nervous system did not venture greatly into new territories after its original flowering, which had greater impact than is now commonly credited. Cajal, by contrast, by the time he was awarded the Nobel Prize, was already breaking new ground with a new staining technique in the field of peripheral nerve regeneration, seeing the reconstruction of a severed nerve by sprouting from the proximal stump as another manifestation of the Neuron Doctrine. Paradoxically, identical studies were going on simultaneously in Golgi's laboratory in the hands of Aldo Perroncito, but the findings did not seem to influence Golgi's thinking on the Neuron Doctrine.
Cells↗
Novel genes expressed in the developing medial cortex.
Two cDNAs, M1 and M2, recently isolated by the differential display method from embryonic rat cerebral hemisphere were characterized and their patterns of spatiotemporal expression analysed in developing rat forebrain by in situ hybridization histochemistry and correlative immunocytochemistry. Neither gene bears any sequence homology to other known genes. Both genes are particularly expressed in medial regions of the cerebral hemisphere and M2 in the roof of the adjacent diencephalon. M1 expression is highly localized and confined to the neuroepithelium of the hippocampal rudiment from embryonic day (E) 12 onward. Its location corresponds to the fimbrial anlage, and immunocytochemical localization of M1 protein indicates its expression in radial glial cells. M2 expression at E12 is more extensive in the medial cerebral wall, extending into the preoptic region and beyond the hippocampus into dorsal hemisphere and into the dorsal diencephalon, with caudal extension along the dorsal midline and in the zona limitans intrathalamica. Later, M2 expression is found in association with the corpus callosum, hippocampal commissure, fimbria, optic nerve, stria medullaris, mamillothalamic tract and habenulopeduncular tract. M1 and M2 expression domains corresponding to the locations of fiber tracts are present prior to the arrival of the earliest axons, as identified by neuron specific markers. These findings suggest M1 and/or M2 genes are involved in early regional specification of the hippocampus and related structures in paramedian regions of the forebrain, and that cell populations expressing these genes in advance of developing axonal pathways may be involved in the early specification of tract location.
Animals↗
Making brain connections: neuroanatomy and the work of TPS Powell, 1923-1996.
Dr. Thomas PS Powell was one of the founders of modern neuroanatomy. His career spanned an era that saw techniques for analyzing connections in the central nervous system dramatically increase in number and resolving power. In tracing the history of his research, one can see how the introduction of each new technique provided an incremental step in analytical capacity although eventually revealing its own limitations. Also evident is the extent to which prejudices born in the days of applying earlier techniques could continue to influence the interpretation of results obtained with new ones. Powell's contributions to neuroscience were extremely wide-ranging, encompassing investigations of the circuitry of the basal ganglia, corticofugal connections, topographic maps in sensory systems, central olfactory pathways, corticocortical and commissural connections, and pathways for sensory convergence in the cerebral cortex. From these investigations, made with tract tracing techniques, much existing knowledge of forebrain organization is derived. He was also one of the earliest investigators to use electron microscopy in the investigation of the central nervous system, and his electron microscopic studies on the olfactory bulb, thalamus, cerebral cortex, and basal ganglia laid, to a large extent, the foundations for all modern research on the synaptic circuitry of these structures. He was given to synthesizing data across systems in order to arrive at common principles of brain organization. A number of these syntheses have been sources of great interest and, occasionally, controversy.
Animals↗
Should a history section be included on the National Youth Sports Program preparticipation physical examination?
The National Youth Sports Program (NYSP) is an annual event sponsored by the National Collegiate Athletic Association that provides structured sports and enrichment programs to youth of low socioeconomic status. As part of the program, youths undergo a free medical examination that uses a physical examination checklist but does not include a section on medical history. To determine what additional information a medical history would provide, a history form was used in conjunction with the regular preparticipation examination for participants in the 1996 NYSP at the North Carolina Agricultural and Technical State University. The history form provided information such as family history of sudden death, personal history of asthma or bone injury, and whether participants took medications or used corrective lenses. Seventy-nine percent of the completed history forms documented a positive response to at least one question. Of these, only 5% had physical findings on examination. Conversely, 15% of participants had physical findings that were not reported on the history form. Because much of what is discovered by a medical history often is not found on physical examination and because history information can be used to prevent the occurrence of an accident or illness, this study suggests that the use of such a form is beneficial in providing a more comprehensive screening.
Adolescent↗
Altered ratios of alternatively spliced long and short gamma2 subunit mRNAs of the gamma-amino butyrate type A receptor in prefrontal cortex of schizophrenics.
The relative abundance of alternatively spliced long (gamma2L) and short (gamma2S) mRNAs of the gamma2 subunit of the gamma-amino butyrate type A (GABAA) receptor was examined in dorsolateral prefrontal cortex of schizophrenics and matched controls by using in situ hybridization histochemistry and semiquantitative reverse transcription-PCR (RT-PCR) amplification. A cRNA probe identifying both mRNAs showed that the transcripts are normally expressed at moderately high levels in the prefrontal cortex. Consistent with previous studies, overall levels of gamma2 transcripts in prefrontal cortex of brains from schizophrenics were reduced by 28.0%, although this reduction did not reach statistical significance. RT-PCR, performed under nonsaturating conditions on total RNA from the same blocks of tissue used for in situ hybridization histochemistry, revealed a marked reduction in the relative proportion of gamma2S transcripts in schizophrenic brains compared with controls. In schizophrenics, gamma2S transcripts had fallen to 51.7% (+/-7.9% SE; P < 0.0001) relative to control levels. Levels of gamma2L transcripts showed only a small and nonsignificant reduction of 16. 9% (+/-12.0% SE, P > 0.05). These findings indicate differential transcriptional regulation of two functionally distinct isoforms of one of the major GABAA receptor subunits in the prefrontal cortex of schizophrenics. The specific reduction in relative abundance of gamma2S mRNAs and the associated relative increase in gamma2L mRNAs should result in functionally less active GABAA receptors and have severe consequences for cortical integrative function.
Adult↗
Thalamic and brainstem contributions to large-scale plasticity of primate somatosensory cortex.
After long-term denervation of an upper limb in macaque monkeys, the representation of the face in somatosensory cortex expands over many millimeters into the silenced representation of the hand. Various brainstem and cortical mechanisms have been proposed to explain this phenomenon. Reorganization in the thalamus has been largely ignored. In monkeys with deafferented upper limbs for 12 to 20 years, it was found that the brainstem cuneate and the thalamic ventral posterior nuclei had undergone severe transneuronal atrophy, and physiological mapping in the thalamus revealed that the face and trunk representations were adjoined while the normally small representation of the lower face had expanded comparable to the expansion in cortex. Reorganization of brainstem and thalamic nuclei associated with slow transneuronal atrophy is likely to be a progressive process. When coupled with divergence of ascending connections, it is likely to make a substantial contribution to representational changes in cortex.
Afferent Pathways↗
Nucleus- and cell-specific expression of NMDA and non-NMDA receptor subunits in monkey thalamus.
Subcortical and corticothalamic inputs excite thalamic neurons via a diversity of glutamate receptor subtypes. Differential expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), kainate, and N-methyl-D-aspartate (NMDA) receptor subunits (GluR1-4; GluR5-7; NR1, NR2A-D) on a nucleus- and cell type-specific basis was examined by quantitative in situ hybridization histochemistry and by immunocytochemical staining for receptor subunits and colocalized gamma-aminobutyric acid (GABA) or calcium binding proteins. Levels of NMDA subunit expression, except NR2C, are higher than for the most highly expressed AMPA (GluR1,3,4) and kainate (GluR6) receptor subunits. Expression of NR2C, GluR2, GluR5, and GluR7 is extremely low. Major differences distinguish the reticular nucleus and the dorsal thalamus and, within the dorsal thalamus, the intralaminar and other nuclei. In the reticular nucleus, GluR4 is by far the most prominent, and NMDA receptors are at comparatively low levels. In the dorsal thalamus, NMDA receptors predominate. Anterior intralaminar nuclei are more enriched in GluR4 and GluR6 subunits than other nuclei, whereas posterior intralaminar nuclei are enriched in GluR1 and differ among themselves in relative NMDA receptor subunit expression. GABAergic intrinsic neurons of the dorsal thalamus express much higher levels of GluR1 and GluR6 receptor subunits than do parvalbumin- or calbindin-immunoreactive relay cells and low or absent NMDA receptors. Relay cells are dominated by NMDA receptors, along with GluR3 and GluR6 subunits not expressed by GABA cells. High levels of NR2B are found in astrocytes. Differences in NMDA and non-NMDA receptor profiles will affect functional properties of the thalamic GABAergic and relay cells.
Animals↗