药物成瘾与中枢结构重塑

药物成瘾是典型的经验依赖性学习记忆过程,其引起的某些行为学和心理学改变可持续终身,这种持久性的改变与成瘾性药物引起的相关神经回路的结构重塑密切相关。本文将简要地回顾并综述吗啡、苯丙胺、可卡因、尼古丁等诱发的特定脑区(如伏核,与激励动机、奖赏效应等有关;前额叶皮层,与决策和行为控制力等相关)神经元树突和树突棘的结构改变,导致突触结构重塑、功能重整。     

Development of basal forebrain projections to visual cortex: Dil studies in rat

We performed experiments using retrograde and anterograde labeling with DiI to examine the development of basal forebrain (BFB) projections to the visual cortex in postnatal rats. DiI placed in occipital cortex led to retrograde labeling of BFB neurons as early as postnatal day 0 (P0); labeled cells were found mainly in the diagonal band complex but also in the medial septum, globus pallidus, and substantia innominata. The retrogradely labeled BFB cells displayed remarkably well-developed dendritic arbors, even in younger animals, and showed increases in soma size, dendritic arbors, and dendritic spines over the first 2 postnatal weeks. Dil placements in the diagonal band led to anterogradely labeled axons in cortex. At early ages (P0–P1), labeled axons were largely confined to white matter. With increasing age, greater numbers of labeled axons were seen in the white matter and in deep cortical layers, and labeled axons extended into superficial layers. The leading edge of labeled fibers reached layer V of visual cortex by P2 and layer IV by P4 and were found throughout the cortical layers by P6. Numbers and densities of labeled axons in visual cortex were greater in older animals, at least through P14. The time of ingrowth of labeled BFB axons into visual cortex indicates that these afferents grow into particular cortical layers after those layers have differentiated from the cortical plate. These data indicate that basal forebrain projections arrive in occipital cortex after cortical lamination is well underway and after the entry of primary thalamocortical projections. © 1995 Wiley-Liss, Inc.     

Sizes of soma and stem dendrites in intracellularly labelled α-motoneurones of the cat

The morphology of identified hindlimb motoneurones was studied after intracellular labelling with Procion yellow (59 cells), Procion red (19 cells) or horseradish peroxidase (9 cells). With respect to the measurements performed, all three intracellular labels gave similar results. As judged by their axonal conduction velocity (62–117 m/sec) all included cells were α-motoneurones. The motoneuronal cell bodies had cross-sectional areas of 816–3732 sq. μm, corresponding to diameters of about 32–69 μm. On average each neurone had 12 (5–20) dendritic stems. For all cells together, the number of dendritic stems per neurone was not strongly correlated to soma diameter. In the whole material, the dendritic stem diameters varied between about 0.5 and 19 μm. Stem dendrites of 4–5 μm were common in all kinds of cells, whereas thicker dendritic stems were preferentially distributed to cells with larger somas. The maximum as well as the mean stem-dendrite diameter (d) per cell was clearly correlated to, and roughly proportional to, the diameter of the cell body. The sum of the cross-sectional areas of all the dendritic stems emanating from a cell (‘sum of dendritic holes’= Σ πd²/4) was roughly proportional to the volume of the soma. Quadriceps motoneurones had a markedly greater number of dendritic stems per cell (mean 16.9) than other kinds of hindlimb motoneurones studied (mean 11.5; includes motoneurones of the hamstring muscles, triceps surae and intrinsic foot muscles). The many quadriceps dendrites were, however, also relatively thin, and the average ratio between ‘sum of dendritic holes’ and soma volume was the same for quadriceps motoneurones as for the other cells.     

The role of matrix metalloproteinases in the morphogenesis of the cerebellar cortex

The morphogenesis of the cerebellar cortex depends on intrinsic genetic programs as well as orchestrated cell-cell/cell-extracellular matrix (ECM) interactions. The matrix metalloproteinase (MMP) family comprises of more than 20 members that catalyze the degradation of all the protein constituents of the ECM. These proteolytic endopeptidases mediate cell-cell/cell-ECM interactions by remodeling the ECM and modulating the activity of membrane-associated receptors. The activity of MMPs is negatively controlled by the tissue inhibitors of metalloproteinases (TIMPs). The MMPs and TIMPs regulate diverse neuronal functions including migration, process extension and synaptic plasticity. MMP-2, -3, -9, membrane type 5-MMP (MT5-MMP), TIMP-1, -2 and -3 are expressed in the developing cerebellum. The spatiotemporal pattern of expression/activity of these enzymes suggests that they play a role in the development of the cerebellar cortex. Blockage of MMP-2/-9 activity by specific inhibitors or blocking antibody, as well as using MMP-9 knock-out mice, clearly establishes that MMP-2/-9 participates in the regulation of morphogenesis of the cerebellum. The potential contributions of these enzymes to granule neuron migration, Purkinje cell dendritogenesis and synaptogenesis are discussed.     

The induction of behavioural sensitization is associated with cocaine-induced structural plasticity in the core (but not shell) of the nucleus accumbens

Repeated exposure to cocaine increases the density of dendritic spines on medium spiny neurons in the nucleus accumbens (Acb) and pyramidal cells in the medial prefrontal cortex (mPFC). To determine if this is associated with the development of psychomotor sensitization, rats were given daily i.p. injections of 15 mg/kg of cocaine (or saline) for 8 days, either in their home cage (which failed to induce significant psychomotor sensitization) or in a distinct and relatively novel test cage (which induced robust psychomotor sensitization). Their brains were obtained 2 weeks after the last injection and processed for Golgi-Cox staining. In the Acb core (AcbC) cocaine treatment increased spine density only in the group that developed psychomotor sensitization (i.e. in the Novel but not Home group), and there was a significant positive correlation between the degree of psychomotor sensitization and spine density. In the Acb shell (AcbS) cocaine increased spine density to the same extent in both groups; i.e. independent of psychomotor sensitization. In the mPFC cocaine increased spine density in both groups, but to a significantly greater extent in the Novel group. Furthermore, when rats were treated at Home with a higher dose of cocaine (30 mg/kg), cocaine now induced psychomotor sensitization in this context, and also increased spine density in the AcbC. Thus, the context in which cocaine is experienced influences its ability to reorganize patterns of synaptic connectivity in the Acb and mPFC, and the induction of psychomotor sensitization is associated with structural plasticity in the AcbC and mPFC, but not the AcbS.     

Morphological properties of respiratory intercostal motoneurons in cats as revealed by intracellular injection of horseradish peroxidase

This study was undertaken to describe details of the location and cellular morphology of functionally identified (inspiratory or expiratory) external and internal intercostal motoneurons on the basis of intracellular injection of horseradish peroxidase (HRP). Sixty HRP-labeled motoneurons were examined; 44 in transverse, 16 in sagittal sections. In the upper thoracic segments (T3-T4), there was only a small overlap in the location of inspiratory external and internal intercostal motoneurons; the inspiratory external motoneurons were generally found more ventromedially within the ventral horn than either inspiratory or expiratory internal intercostal motoneurons. No major morphological differences were observed between the types of motoneurons studied. The number of primary dendrites ranged from 6 to 10. The dendrites projected mainly along the medial or the lateral border of the ventral horn, and rostrocaudally up to 1,760 micron from the cell body. The paths taken by dendrites to fill the territory occupied by the dendritic trees appeared to depend upon location of the cell body. Few dendrites penetrated the white matter. Axon diameters varied from 1.1 to 6.7 micron (mean 3.6 +/- 1.3 micron, n = 55). Collateral branches were identified in 78% of axons. The number of branches arising from a given axon varied from 1 to 4. It is concluded that the respiratory intercostal motoneurons form a morphologically homogeneous population, in spite of their functional differences.     

Age-related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET)

Muscarinic cholinergic M1 and M2 receptors in young and aged adult male volunteers were studied using [N-11C-methyl]-benztropine, a specific muscarinic cholinergic receptor ligand, and high resolution positron emission tomography (PET). A regionally specific pattern of decreased binding was observed in aged volunteers. Using two separate methods of data analysis, thalamic, hippocampal and cerebellar regions showed no decreases in the apparent specific binding of [N-11C-methyl]-benztropine while frontal, parietal, temporal and occipital cortices as well as the corpus striatum showed age related changes in binding that declined (in 82 yrs old subject) to about 50% of the value obtained from the youngest volunteer (19 yrs). These data suggest that regions high in muscarinic receptor density, the corpus striatum and the cortical mantle, show a greater rate of decline than those areas that have a relatively low number of muscarinic receptors. Furthermore, this study demonstrates the usefulness of PET and [N-11C-methyl]-benztropine for assessing age related regional changes in muscarinic cholinergic receptor binding in the living human brain.     

Phrenic motoneuron morphology in the neonatal rat.

The morphology of neonatal rat phrenic motoneurons was studied following retrograde labeling with horseradish peroxidase, which resulted in Golgi-like fills of phrenic motoneuron somata and dendrites. At birth, these neurons have well-developed dendritic trees with many characteristics described for phrenic motoneurons in the adult rat. The dendrites form tightly fasciculated bundles that emerge from the phrenic nucleus primarily along four axes: ventromedial, ventrolateral, dorsolateral, and rostral/caudal, with smaller and more variable projections directly lateral and ventral. Although sparse, some dendritic appendages were also present, and in a few animals, somata clustering was apparent. The most significant difference between adult and neonatal rat phrenic motoneurons is in the extent to which medially and laterally projecting dendrites extend beyond the borders of the ipsilateral gray matter. In the neonate, unlike the adult, these dendrites project extensively past the gray/white border to the edge of the hemicord. Ventromedial dendrites occasionally cross to the contralateral ventral horn in the ventral white commissure and laterally projecting dendrites could be seen reaching the edge of the cord, turning and traveling rostrally or caudally for up to 100 microns. Phrenic motoneurons are not unique in having long dendrites at birth. A brief comparative study showed that neonatal cervical, thoracic, and lumbar motoneurons also have long dendrites that project to the medial and lateral borders of the hemicord.