切割穹窿海马伞大鼠海马内Brn-4 mRNA的表达变化——原位杂交法

目的 探讨大鼠穹隆海马伞切割侧与正常侧海马内Brn-4 mRNA表达的差异.方法 切割大鼠右侧穹窿海马伞,切割后14d制备海马冰冻切片,用体外转录法制备地高辛标记的Brn-4 RNA探针进行原位杂交.每只动物随机计数3张切片切割侧和正常侧Brn-4 mRNA的阳性细胞,测定其吸光度(A)值,进行配对t检验分析.结果 切割侧和正常侧海马锥体细胞层和齿状回颗粒层均见Brn-4 mRNA阳性细胞,两侧细胞数无明显差异,但切割侧阳性细胞平均吸光度值较正常侧明显增加(P＜0.01);而在齿状回门区和颗粒下层,切割侧Brn-4 mRNA阳性细胞数和平均吸光度值均较正常侧升高(均P＜0.01).结论 穹窿海马伞切割侧海马锥体细胞层和齿状回颗粒层细胞中Brn-4 mRNA的表达量明显增强,而在齿状回门区和颗粒下层中,其阳性细胞数和表达量均较正常侧明显升高.结合本课题组以往的工作,提示切割穹窿海马伞后,海马中Brn-4 mRNA表达的增高可能与促进其中的神经干细胞向神经元分化有关.     

大鼠隔区AChE阳性神经元向海马的投射

本文用改良AChE组化法和Nissl法研究了切断大鼠-侧伞-穹窿后的隔区和海马内的细胞之胞体和纤维的形态改变.结果显示:术后第5天,在Nissl染色切片上术侧隔区细胞肿胀、皱缩,或染质溶解,或胶质增生,或细胞数减少.AChE染色显示术侧隔区AChE阳性细胞增大、或皱缩或数减少.术侧海马区AChE阳性纤维明显减少.第10天和第15天,上述变化进一步加剧.本实验证实隔区AChE阳性神经元大部分发支经伞-穹窿投射至海马.     

切割穹窿海马伞大鼠海马内Lhx8 mRNA表达的变化

目的:探讨切割穹窿海马伞大鼠切割侧与正常侧海马内Lhx8 mRNA表达的差异。方法:切割SD大鼠右侧穹窿海马伞。切割后7d制备海马冰冻切片,用体外转录法制备地高辛标记的Lhx8 RNA探针进行原位杂交,分析切割侧和正常侧海马锥体细胞层和齿状回颗粒层中及齿状回门区和颗粒下层中的Lhx8 mRNA阳性细胞的数量和平均光密度值。结果:切割侧和正常侧海马锥体细胞层和齿状回颗粒层Lhx8 mRNA阳性细胞数量无明显差异,但切割侧平均光密度值较正常侧明显增加;在齿状回的门区和颗粒下层,切割侧Lhx8 mRNA阳性细胞数和平均光密度值均较正常侧升高。结论:切割穹窿海马伞后海马中Lhx8 mRNA表达上调,可能与其中的神经干细胞向胆碱能神经元分化的神经再生机制有关。     

Jagged1在大鼠切割穹窿海马伞后海马内的表达变化

目的:探讨切割穹窿海马伞后不同时相点海马内Jagged1的动态表达变化。方法:切割SD大鼠双侧穹窿海马伞,于切割后第3、7、14、21 d分别提取海马组织总RNA和总蛋白,应用RT-PCR和Western Blot的方法分别检测Jagged1基因和蛋白的表达变化;切割SD大鼠右侧穹窿海马伞,7 d后通过免疫组织化学的方法检测海马齿状回颗粒下层和门区中Jagged1阳性细胞的数目和平均光密度值(MOD)。结果:Jagged1基因和蛋白在切割穹窿海马伞后的第3 d表达开始增高,第7 d时达到最高水平,第14 d后表达下降至正常水平;切割穹窿海马伞后的第7 d,切割侧海马齿状回颗粒下层和门区中Jagged1阳性细胞数为167.89±22.11,平均光密度值为0.11±0.02;正常侧阳性细胞数为140.45±22.63,平均光密度值为0.06±0.01;切割侧阳性细胞数和平均光密度值与正常侧均明显增高(P0.05)。结论:切割穹窿海马伞后Jagged1基因和蛋白的表达呈现出先增高后降低的变化趋势,提示Jagged1是切割穹窿海马伞后海马内微环境的重要组成分子。     

切割穹窿海马伞大鼠海马内BLBP的表达变化

为了观察切割大鼠右侧穹窿海马伞后,切割侧与正常侧海马齿状回内脑脂结合蛋白(BLBP)的表达变化,本研究应用Western blot和免疫组织化学方法检测双侧海马内BLBP蛋白表达水平的变化,以及海马齿状回门区和颗粒下层中BLBP免疫阳性细胞数和灰度值。结果显示:正常大鼠双侧海马各区和颗粒下层细胞BLBP仅有微量表达,切割穹窿海马伞后第1 d双侧差异不明显;3 d时切割侧颗粒下层阳性细胞及染色深度较正常侧加深;5 d时切割侧颗粒下层阳性细胞数量明显增多,染色较深,并达到最高水平;7 d后BLBP免疫阳性细胞的数量和染色深度开始降低,14 d时接近正常侧水平。而切割后3、5 d时双侧门区BLBP免疫阳性细胞的数量差异不大,但切割侧染色较深,7 d后也逐渐降低,14 d时降至正常侧水平。上述结果提示,切割穹窿海马伞阻断了隔区与海马齿状回的纤维联系后,可引起海马齿状回门区和颗粒下层BLBP表达增强,可能引发了放射状胶质细胞的增殖和激活,构成的支架有助于神经干细胞的迁移和向神经元的分化。     

NOV蛋白在切割海马伞大鼠海马中表达的变化

通过切割右侧海马伞制备大鼠海马伞损伤模型,应用Westernblotting、免疫组织化学技术,观察切割海马伞后不同时程海马中肾母细胞瘤过度表达基因(NOV)蛋白表达的变化,并对结果进行图像处理和统计学分析。Westernblotting结果显示,NOV蛋白在切割海马伞后3d表达开始上升,14d达高峰后缓慢下降。切割海马伞后14d切割侧和正常侧相比较,海马CA1-CA3区的锥体细胞层及齿状回颗粒层NOV阳性细胞数目无显著性差异(P>0.05),但切割侧NOV阳性细胞明显比正常侧深染,两侧比较平均灰度值有显著性差异(P<0.01)。结合本课题组以往的工作,本研究结果提示,切割海马伞后海马中高表达的NOV蛋白可能参与了诱导神经干细胞迁移和向神经元分化的过程。     

穹窿海马伞损伤对大鼠学习记忆和海马GFAP阳性神经胶质细胞的影响

为探讨穹隆海马伞损伤鼠学习记忆能力与海马胶质纤维酸性蛋白阳性细胞之间的关系 ,切断 SD成年大鼠左侧穹窿海马伞 ,用 Y迷宫和免疫组织化学结合图像分析系统测试大鼠学习记忆能力和海马胶质纤维酸性蛋白阳性细胞的变化状况及它们的相互关系。结果显示 :损伤 2周后 ,损伤组损伤侧海马 CA1 区辐射层和齿状回分子层胶质纤维酸性蛋白阳性细胞的数密度较正常组分别增多 3 0 .2 9%和 3 0 .15 % (都为 P<0 .0 1) ,胞体面积分别增加 16.0 4%和 19.42 % (都为 P<0 .0 1) ,齿状回分子层胶质纤维酸性蛋白阳性细胞体密度增大 19.40 % (P<0 .0 5 )。经相关分析 ,大鼠学习记忆能力与海马 CA1 区胶质纤维酸性蛋白阳性细胞数密度呈负相关 (r=-0 .83 6,P<0 .0 1) ,与齿状回数密度呈负相关 (r=-0 .792 ,P<0 .0 1)。提示海马星形胶质细胞可能参与学习记忆过程     

切割穹窿海马伞后海马齿状回内Lhx8的表达变化及其对RGCs向胆碱能神经元分化的影响

目的:明确Lhx8在SD大鼠切割穹窿海马伞后海马齿状回颗粒下层和门区中的表达变化。方法:切割SD大鼠穹窿海马伞,成功制备海马去神经支配动物模型后,通过Western Blot的方法检测切割后第1、3、7、14、21、28 d海马中Lhx8蛋白的表达变化;通过免疫组织化学方法检测切割后第7天海马齿状回颗粒下层和门区中Lhx8阳性细胞的表达定位,并通过免疫荧光化学方法检测Lhx8/ChAT双标阳性细胞的共定位情况;切割SD大鼠穹窿海马伞并制备海马提取液,将其加入至细胞培养液中,模拟体内海马神经再生微环境,检测培养的海马放射状胶质细胞(radial slia cells,RGCs)向胆碱能神经元分化的情况。结果:切割穹窿海马伞后第7 d,Lhx8蛋白表达量较其他各时相点明显增高;海马齿状回颗粒下层和门区中Lhx8阳性细胞数目和光密度也明显高于正常侧,Lhx8/ChAT双标阳性细胞数目也较正常侧增多;体外细胞培养,切割穹窿海马伞侧海马提取液也较正常侧海马提取液更能促进海马放射状胶质细胞向胆碱能神经元的分化。结论:切割穹窿海马伞后,Lhx8表达明显上调,与海马齿状回的胆碱能神经再生有关。     

PEBP在切割穹窿海马伞大鼠海马中的表达变化

切割大鼠右侧穹窿海马伞,应用Western blot、免疫组化技术,观察切割后海马中磷脂酰乙醇胺结合蛋白(phosphatidyle-thanolamine binding protein,PEBP)的表达的时空变化。Western blot结果显示:PEBP在切割后3 d表达开始上升,7 d达最高水平,随后缓慢下降,28 d时降至正常。免疫组化结果显示:术后各时间点切割侧海马CA1～CA3区的锥体细胞层和齿状回颗粒层的PEBP阳性细胞数与正常侧相比无显著性差异(P>0.05),但切割侧PEBP阳性细胞染色加深,7 d时最为明显,两侧比较灰度值有显著性差异(P<0.01)。切割侧齿状回门区和颗粒下层中可见较多深染的PEBP阳性细胞,其细胞数和灰度值与正常侧相比均有显著性差异(P<0.05)。结合本课题组以往的工作,本结果提示切割穹窿海马伞后PEBP的高表达可能与海马神经再生有关。     

穹窿海马伞切割后大鼠海马伞内神经干细胞的观察研究

目的观察穹窿海马伞切割侧和非切割侧大鼠海马伞内神经干细胞的表达情况。方法切割SD大鼠右侧穹窿海马伞,于术后2d经腹腔注射BrdU,连续5d,术后7d取脑冰冻切片,进行BrdU/Nestin免疫荧光双标检测。结果穹窿海马伞切割侧海马伞内的BrdU阳性细胞数和Nestin阳性细胞数均明显多于非切割侧,且出现较多的BrdU/Nestin双标的阳性细胞,而非切割侧未见BrdU/Nestin双标的阳性细胞。结论穹窿海马伞切割后,切割侧海马伞内出现较多增殖的神经干细胞,我们推测海马伞的损伤,导致海马伞内局部微环境发生变化,产生某些信号物质,刺激脑内其他部位的神经干细胞增殖并迁移到海马伞内。     

Effects of fimbria-fornix transection on calpain and choline acetyl transferase activities in the septohippocampal pathway

The ability of fimbria-fornix bilateral axotomy to elicit calpain and caspase-3 activation in the rat septohippocampal pathway was determined using antibodies that selectively recognize either calpain- or caspase-cleaved products of the cytoskeletal protein alphaII-spectrin. Radioenzymatically determined choline acetyl transferase (ChAT) activity was elevated in the septum at day 5, but reduced in the dorsal hippocampus at days 3, 5 and 7, after axotomy. Prominent accumulation of calpain-, but not caspase-3-, cleaved spectrin proteolytic fragments was observed in both the septum and dorsal hippocampus 1-7 days after axotomy. ChAT-positive neuronal cell bodies in the septum also displayed calpain-cleaved spectrin indicating that calpain activation occurred in cholinergic septal neurons as a consequence of transection of the septohippocampal pathway. Calpain-cleaved alphaII-spectrin immunoreactivity was observed in cholinergic fibers coursing through the fimbria-fornix, but not in pyramidal neurons of the dorsal hippocampus, suggesting that degenerating cholinergic nerve terminals were the source of calpain activity in the dorsal hippocampus following axotomy. Accumulation of calpain-cleaved spectrin proteolytic fragments in the dorsal hippocampus and septum at day 5 after axotomy was reduced by i.c.v. administration of two calpain inhibitors. Calpain inhibition partially reduced the elevation of ChAT activity in the septum produced by transection but failed to decrease the loss of ChAT activity in the dorsal hippocampus following axotomy. These findings suggest that calpain activation contributes to the cholinergic cell body response and hippocampal axonal cytoskeletal degradation produced by transection of the septohippocampal pathway.     

The phospholipase A2 inhibitor quinacrine prevents increased immunoreactivity to cytoplasmic phospholipase A2 (cPLA2) and hydroxynonenal (HNE) in neurons of the lateral septum following fimbria-fornix transection

The distribution of cytoplasmic phospholipase A₂ (cPLA₂), 4-hydroxynonenal (HNE), and choline acetyltransferase (ChAT) was studied in the septum and hippocampus of rats at various time intervals after fimbria-fornix (FF) transection. Very little cPLA₂ or HNE immunoreactivity was observed in the normal medial or lateral septum, whereas a large increase in immunoreactivity with both antibodies was observed in the lateral septum one week after transection. The increase in cPLA₂ or HNE staining in the lateral septum after FF transection was completely blocked by intraperitoneal injections (once daily) of a lipophilic inhibitor of phospholipase A₂, quinacrine (5 mg/kg), showing the importance of phospholipase A₂ in generation of arachidonic acid, which is a target for lipid peroxidation and formation of 4-hydroxynonenal. Quinacrine prevented not only a rise in HNE immunoreactivity, but also a rise in cPLA₂ immunoreactivity, showing that cPLA₂ expression itself is depressed by the drug, in addition to its well-known effect on blocking the catalytic action of phospholipase A₂. No increase in cPLA₂ or HNE immunoreactivity was observed in neurons of the medial septum after fimbria-fornix transection, even though these showed a decrease in ChAT staining after the lesion. This suggests that glutamate released from transected hippocamposeptal afferents or increased activity of the supramammillary area following FF transection may lead to increased cPLA₂ and HNE immunreactivity, whereas retrograde degeneration in neurons may not. We conclude that there is free-radical damage, as evidenced by HNE formation in neurons of the lateral septum after fimbria-fornix transection, and that this increase in HNE is dependent on phospholipase A₂ activity. Electronic Publication     

Cholinergic neurons in the rat hippocampus do not compensate for the loss of septohippocampal cholinergic fibers

In recent studies a small number of choline acetyltransferase (ChAT)-immunoreactive, supposedly cholinergic, neurons intrinsic to the rat hippocampus have been described. Here we report that these neurons are not capable of sprouting in response to removal of the cholinergic input to the hippocampus from the medial septum/diagonal band complex. One month after unilateral transection of the fimbria-fornix an almost complete lack of cholinergic fibers persists in all layers of the dorsal hippocampus and fascia dentata ipsilateral to the lesion when compared to the contralateral hippocampus or to unlesioned control rats. These results indicate that the well-known phenomenon of collateral sprouting in response to partial deafferentation is a specific process that spares a distinct group of cholinergic cells in the rat hippocampus.     

The effects of hippocampal and fimbria-fornix lesions on prepulse inhibition

The present experiments tested the effects of conventional (dorsal aspiration and electrolytic) and excitotoxic (N-methyl-D-aspartate [NMDA]) hippocampal lesions and fimbria-fornix (FF) transection on prepulse inhibition (PPI) of startle response and on open-field activity. Activity was increased by FF transection and by conventional but not excitotoxic hippocampal lesions; complete NMDA lesion increased amphetamine-induced activity. Whereas dorsal hippocampal aspiration lesion disrupted PPI, the phenomenon was not affected by dorsal hippocampal electrolytic lesion, partial or complete excitotoxic (NMDA) hippocampal lesions, or complete FF transection, which interrupted the cholinergic input to the hippocampus as well as the hippocampal-subicular input to the nucleus accumbens. Systemic apomorphine disrupted PPI in both FF-transected rats and their controls. It is suggested that the hippocampus is essential for PPI disruption rather than for PPI expression.     

Embryonic intermediate filament,nestin, expression following traumatic spinal cord injury in adult rats

Precursor cells in the ependyma of the lateral ventricles of adult mammalian brain have been reported in brain, and also in the spinal cord. The present study used antibody to the intermediate filament protein (nestin) as an immunohistochemical marker for neural stem cells and precursor cells in a rat model of spinal cord trauma. Male Sprague-Dawley rats (n=25) had a laminectomy at Thll-Thl2, and spinal cord contusion was created by compression with 30 g of force for 10 min. The rats were killed at 24 h, 1 week and 4 weeks after injury, and four levels of the spinal cord were examined: 5 mm and 10 mm, both rostral and caudal region to the injury center. Time- and region-dependent alterations of nestin immunoreactivity were analyzed. Revealed at 24 h post-injury, 5 mm rostral and caudal to the lesions, nestin expression was observed in ependymal cells and around the hemorrhagic and necrotic lesion located in dorsal spinal cord, peaking at 1 week after injury. Moreover, nestin expression was also observed in the white matter of ventral spinal cord, extending into arborizing processes centripetally from the pial surface toward the central canal. At 4 weeks after injury, nestin expression in ependyma decreased 10 mm from the injury site. But nestin expression in white matter increased dramatically with a 100-fold increase in nestin originating from the pial surface, and extension now to all the white matter. The latter was accompanied by glial fibrillary acidic protein positivity into very long arborizing processes, morphologically compatible with radial glia. The findings suggest two possible sources of precursor cells in adult mammalian spinal cord; ependyma of the central canal and subpial astrocytes. Subpial astrocytes may be associated with neural repair and regeneration after spinal cord injury.     

Alzheimer病模型大鼠脑组织c-fos基因的表达

为了研究手术切断穹窿 -海马伞所建立的 Alzheimer病模型大鼠脑组织中原癌基因 c-fos的表达状况 ,于建模后 1h、6d和 15 d对大鼠进行灌注固定 ,取含海马结构的脑组织分别进行 H-E染色和 FOS蛋白的免疫组化反应 ;同时于建模前后对大鼠进行电迷宫检查。结果表明 :FOS样免疫活性在 Alzheimer大鼠的海马及大脑皮层均有增强 ,并随术后时间的延长有不断增强的趋势 ,因而认为这种 Alzheimer模型可以模拟出与 AD患者类似的 c-fos过度表达     

Acetylcholine release in the rat hippocampus as studied by microdialysis is dependent on axonal impulse flow and increases during behavioural activation

Changes in extracellular levels of acetylcholine and choline in the hippocampal formation were measured using intracerebral microdialysis coupled to high performance liquid chromatography with post-column enzyme reaction and electrochemical detection. Various pharmacological and physiological manipulations were applied to awake unrestrained normal rats and rats subjected to a cholinergic denervation of the hippocampus by a complete fimbria-fornix lesion (1-2 weeks previously). Low baseline levels of acetylcholine (about 0.3 pmol/15 min sample) could be detected in the absence of acetylcholinesterase inhibition in all animals. However, in order to obtain stable and more readily detectable levels, the acetylcholinesterase inhibitor neostigmine was added to the perfusion medium at a concentration of 5 or 10 microM and was used during all subsequent manipulations. Addition of neostigmine increased acetylcholine levels approximately 10-fold (to 3.7 pmol 15 min) in the normal rats, which was about 4-fold higher than the levels recovered from the denervated hippocampi. Depolarization by adding KCl (100 mM) to the perfusion fluid produced a 3-fold increase in the extracellular acetylcholine levels, and the muscarinic antagonist atropine (3 microM) resulted in a 4-fold increase in the normal rats, whereas these drugs induced only small responses in the denervated rats. Neuronal impulse blockade by tetrodotoxin (1 microM) resulted, in normal rats, in a 70% reduction in extracellular acetylcholine levels. Sensory stimulation by handling increased acetylcholine levels by 94% in the normal rats, whereas this response was almost totally abolished in the denervated hippocampi. Behavioural activation by electrical stimulation of the lateral habenula resulted in a 4-fold increase in acetylcholine release in normal animals, and this response was totally blocked by a transection of the lateral habenular efferents running in the fasciculus retroflexus. The levels obtained by lateral habenula stimulation were reduced by about 95% in the rats with fimbria-fornix lesions. Following an acute knife transection of the fimbria-fornix performed during ongoing dialysis, acetylcholine levels dropped instantaneously by 70%, indicating that the extracellular acetylcholine levels in the hippocampus are maintained by a tonic impulse flow in the septohippocampal pathway. The extracellular levels of choline were reduced by about 30% after the addition of neostigmine in the normal rats, and increased by about 50% in both normal and denervated rats after addition of KCl to the perfusion fluid. No changes could be detected after atropine, handling, lateral habenula stimulation, or acute fimbria-fornix or fasciculus retroflexus transection.(ABSTRACT TRUNCATED AT 400 WORDS)     

Behaviour-dependent changes in acetylcholine release in normal and graft-reinnervated hippocampus: evidence for host regulation of grafted cholinergic neurons.

Grafted neurons obtained from the fetal basal forebrain can provide a functional cholinergic reinnervation of the hippocampal formation in rats with a lesion of the intrinsic septal cholinergic afferents. In the present experiments graft-derived acetylcholine release in the hippocampus was studied by microdialysis in awake rats during different types of behaviours which are known to activate the innate septohippocampal cholinergic system and during different activity periods of the day-night cycle. Two types of basal forebrain grafts were studied: cell suspensions implanted into the hippocampus in rats with an aspirative lesion of the fimbria-fornix, and grafts of solid tissue implanted as a tissue bridge into the fimbria-fornix lesion cavity. Increased acetylcholine overflow was seen in both groups with grafts during sensory stimulation (by handling). The strongest response (50% increase in acetylcholine release) was seen in rats with solid basal forebrain grafts (equivalent to two-thirds of that seen in intact rats). Immobilization stress and motor activity (swimming) also resulted in increased, but more variable, acetylcholine release (+ 30%; about one-third of the normal response). None of these effects was seen in the control rats with fimbria-fornix lesion only. The two-fold difference in hippocampal acetylcholine release in normal animals between day and night was absent in both types of grafted rats. An acute knife-cut, transecting the connections between the solid basal forebrain graft and the host hippocampus, caused an immediate 75% reduction in acetylcholine release (similar to the effect of an acute fimbria-fornix transection in the normal rats) and the response to swimming was no longer evident. The results show that grafted cholinergic neurons can be functionally integrated into the host brain, allowing the grafted neurons to be activated in the correct behavioural contexts, although the changes in acetylcholine overflow were overall smaller and more variable than normal. The ability of the host to influence cholinergic graft activity, most probably mediated via activation of afferent host-graft connections, may contribute to the efficacy of basal forebrain grafts in the amelioration of behavioural impairments in animals with lesions of the forebrain cholinergic system.     

Retrograde cell changes in medial septum and diagonal band following fimbria-fornix transection: quantitative temporal analysis

Complete unilateral fimbria-fornix transections, including the overlying cingulate cortex, were administered to female rats. At time points from 1 day to 6 weeks, the septal-diagonal band region was examined using acetylcholinesterase histochemistry, Cresyl Violet cell staining, and choline acetyltransferase biochemistry. As early as 1 day following the transection a decrease in acetylcholinesterase positive cell body staining was observed in the medial septum; however, no loss of Nissl-stained neurons was measured in Cresyl Violet stained sections until 1 week after the lesion. Maximal loss of acetylcholinesterase-positive cells, as visualized after irreversible acetylcholinesterase inhibition, was measured at 1 week, and no further change was observed at time points up to 6 weeks after operation. The loss of acetyltransferase-positive cells was greatest in the medial septal area (-65%) and the vertical limb of the diagonal band (-55%). Little cell loss was measured in the horizontal limb of the diagonal band. This is consistent with the known projections of these cell bodies. Remaining acetylcholinesterase-positive cell bodies in the medial septum had shrunk by about 20% (measured as the diameter along the major axis). A marked neuronal cell loss (about 50%) was demonstrable in the medial septum and vertical limb of the diagonal band in the Cresyl Violet-stained sections, too. A pile-up of acetylcholinesterase-stained material was observed in the dorsal-lateral quadrant of the septal area just proximal to the lesion at 1 day following transection. This pile-up occurred in the medial septum and diagonal band area up to 1 week following the transection, and had nearly disappeared by 2 weeks post-transection. Choline acetyltransferase biochemical activity, measured in samples of whole septum, decreased significantly at 1 day but subsequently returned to control levels. By 2 weeks following transection, an increase in acetylcholinesterase-positive stained fibers was observed in the dorsal-lateral quadrant of the septum, ipsilateral to the lesion relative to the contralateral septum. This response, which was interpreted as sprouting from the lesioned axons proximal to the transection, probably accounted for the rise in choline acetyltransferase biochemical activity in the whole septum following the reduction on the first day.