Olfactory learning modifies predisposition for long-term potentiation and long-term depression induction in the rat piriform (olfactory) cortex

Learning-related modifications in predisposition for long-term potentiation (LTP) and long-term depression (LTD) were studied in brain slices of the rat piriform cortex following olfactory learning. Rats were trained to discriminate between pairs of odors until they demonstrated rule learning. We have previously shown that such training is accompanied by enhanced neuronal excitability and increased synaptic transmission in the intrinsic synaptic pathway. Here we show that the susceptibility for further enhancing synaptic connectivity by inducing LTP in slices from trained rats is markedly reduced after training, compared with slices from pseudo-trained and naive rats. Accordingly, while 900 stimuli at 1 Hz did not induce LTD in slices from control rats, it induced significant LTD in slices from trained rats. Post-tetanic potentiation (PTP) was also reduced after training, indicating that synaptic release is enhanced after odor learning, as previously suggested. We suggest that learning-related cellular modifications and activity-dependent synaptic plasticity share a common mechanism in the primary olfactory cortex. Our data also support the prediction generated according to the sliding modification threshold theory that learning should be accompanied by reduced capability of inducing LTP and increased susceptibility for LTD induction.     

Contribution of Ih to neuronal damage in the hippocampus after traumatic brain injury in rats

Traumatic brain injury (TBI) causes selective neuronal damage in the hippocampus; however, the underlying mechanisms are still unclear. Post-traumatic alterations of ion channel activity, which actively regulate neuronal excitability and thus impact on excitotoxicity, may be involved in TBI-induced neuronal injury. Here we report that hyperpolarization-activated cation current (I(h)) contributes to the distinct vulnerability of hippocampal neurons in TBI. In a rat model of controlled cortical injury, moderate TBI produced neuronal death of both hippocampal CA3 neurons and mossy cells in the hilus, but not CA1 pyramidal cells. Treatment with lamotrigine, which enhances dendritic I(h), ameliorated TBI-induced neuronal damage to CA3 neurons and mossy cells. In contrast, intraventricular administration of I(h) channel blocker caused cell death in the CA1 region after TBI. Whole-cell recordings revealed that, differently from CA3 neurons, CA1 pyramidal cells expressed larger I(h) and exhibited a post-traumatic increase of I(h) amplitude. Moreover, blocking I(h) led to an increase of neuronal excitability, with greater effects seen in post-traumatic CA1 pyramidal cells than in CA3 neurons. In addition, the I(h) in mossy cells was dramatically inhibited early after TBI. Our findings indicate that differential changes of I(h) in hippocampal neurons may be one of the mechanisms of selective cell death, and that an enhancement of functional I(h) may protect hippocampal neurons against TBI.     

Alterations of A-type potassium channels in hippocampal neurons after traumatic brain injury

Traumatic brain injury (TBI) is associated with cognitive deficits, memory impairment, and epilepsy. Previous studies have reported neuronal loss and neuronal hyperexcitability in the post-traumatic hippocampus. A-type K+ currents (I(A)) play a critical role in modulating the intrinsic membrane excitability of hippocampal neurons. The disruption of I(A) is reportedly linked to hippocampal dysfunction. The present study investigates the changes of I(A) in the hippocampus after TBI. TBI in rats was induced by controlled cortical impact. The impact induced a reproducible lesion in the cortex and an obvious neuronal death in the ipsilateral hippocampus CA3 region. At one week after TBI, immunohistochemical staining and Western blotting showed that the expression of I(A) channel subunit Kv4.2 was markedly decreased in the ipsilateral hippocampus, but remained unchanged in the contralateral hippocampus. Meanwhile, electrophysiological recording showed that I(A) currents in ipsilateral CA1 pyramidal neurons were significantly reduced, which was associated with an increased neuronal excitability. Furthermore, there was an increased sensitivity to bicuculline-induced seizures in TBI rats. At 8 weeks after TBI, immunohistochemical staining and electrophysiological recording indicated that I(A) returned to control levels. These findings suggest that TBI causes a transient downregulation of I(A) in hippocampal CA1 neurons, which might be associated with the hyperexcitability in the post-traumatic hippocampus, and in turn leads to seizures and epilepsy.     

Transplantation of rat synapsin-EGFP-labeled embryonic neurons into the intact and ischemic CA1 hippocampal region: distribution, phenotype, and axodendritic sprouting

A major limitation of neural transplantation studies is assessing the degree of host-graft interaction. In the present study, rat hippocampal/cortical embryonic neurons (E18) were infected with a lentivirus encoding enhanced green fluorescent protein (GFP) under control of the neuron-specific synapsin promoter, thus permitting robust identification of labeled neurons after in vivo grafting. Two weeks after transient forebrain ischemia or sham-surgery, GFP-expressing neurons were transplanted into CA1 hippocampal regions in immunosuppressed adult Wistar rats. The survival, distribution, phenotype, and axonal projections of GFP-immunoreactive (IR) positive transplanted neurons were evaluated in the sham-operated and ischemia- damaged CA1 hippocampal regions 4, 8, and 12 weeks after transplantation. In both experimental groups, we observed that the main phenotype of host-derived afferents projecting towards grafted GFP-IR neurons as well as transplant-derived GFP-IR efferents were glutamatergic in both animal groups. GFP axonal projections were seen in the nucleus accumbens, septal nuclei, and subiculum-known target areas of CA1 pyramidal neurons. Compared to sham-operated animals, GFP-IR neurons grafted into the ischemia-damaged CA1 migrated more extensively throughout a larger volume of host tissue, particularly in the stratum radiatum. Moreover, enhanced axonal sprouting and neuronal plasticity of grafted cells were evident in the hippocampus, subiculum, septal nuclei, and nucleus accumbens of the ischemia-damaged rats. Our study suggests that the adult rat brain retains some capacity to direct newly sprouting axons of transplanted embryonic neurons to the correct targets and that this capacity is enhanced in previously ischemia-injured forebrain.     

Depression of human corticospinal excitability induced by magnetic theta-burst stimulation: evidence of rapid polarity-reversing metaplasticity

Metaplasticity refers to the activity-dependent modification of the ability of synapses to undergo subsequent potentiation or depression, and is thought to maintain homeostasis of cortical excitability. Continuous magnetic theta-burst stimulation (cTBS; 50 Hz-bursts of 3 subthreshold magnetic stimuli repeated at 5 Hz) is a novel repetitive magnetic stimulation protocol used to model changes of synaptic efficacy in human motor cortex. Here we examined the influence of prior activity on the effects induced by cTBS. Without prior voluntary motor activation, application of cTBS for a duration of 20 s (cTBS300) facilitated subsequently evoked motor potentials (MEP) recorded from APB muscle. In contrast, MEP-size was depressed, when cTBS300 was preceded by voluntary activity of sufficient duration. Remarkably, even without prior voluntary activation, depression of MEP-size was induced when cTBS was extended over 40 s. These findings provide in vivo evidence for extremely rapid metaplasticity reversing potentiation of corticospinal excitability to depression. Polarity-reversing metaplasticity adds considerable complexity to the brain's response toward new experiences. Conditional dependence of cTBS-induced depression of corticospinal excitability on prior neuronal activation suggests that the TBS-model of synaptic plasticity may be closer to synaptic mechanisms than previously thought.     

The aging hippocampus: cognitive, biochemical and structural findings

Aging is often accompanied by learning and memory problems, many of which resemble deficits associated with hippocampal damage. Studies of aging in nonhuman animals have demonstrated hippocampus-related memory decline, and point to a possible locus for impairments associated with normal and pathological aging in humans. Two well-characterized hippocampus-dependent tasks in nonhuman animal literature are the Morris water task (MWT) and the transverse patterning discrimination task (TPDT). We employed the virtual MWT and the TPDT to assess hippocampus-dependent cognition in humans. Magnetic resonance imaging and proton magnetic resonance spectroscopy were employed to measure hippocampal volume and neurochemistry respectively. Age-related deficits were observed in performance on both hippocampus-dependent tasks. This pattern of impairment was accompanied by decreased hippocampal NAA/Cre ratios and volume, both of which imply neuronal loss and/or decrease in neuronal density. Collectively, our results suggest that hippocampus undergoes structural and biochemical changes with normal aging and that these changes may represent an important component of age-related deterioration in hippocampus-dependent cognition.     

Bell-shaped D-serine actions on hippocampal long-term depression and spatial memory retrieval

D-Serine, the endogenous coagonist of N-methyl-D-aspartate receptors (NMDARs), is considered to be an important gliotransmitter, and is essential for the induction of long-term potentiation. However, less is known about the role of D-serine in another form of synaptic plasticity, long-term depression (LTD). In this study, we found that exogenous D-serine regulated LTD in the hippocampal CA1 region in a "bell-shaped" concentration-dependent manner through regulating the function of NMDARs in the same manner, whereas endogenous D-serine was activity-dependently released and, in turn, contributed to the induction of LTD during low-frequency stimulation. Furthermore, impairing glial functions with sodium fluoroacetate (NaFAC) reduced the magnitude of LTD, which could be restored by exogenous D-serine, indicating that endogenous D-serine is mainly glia-derived during LTD induction. More interestingly, similar to the effects on LTD, exogenous D-serine enhanced spatial memory retrieval in the Morris water maze in a bell-shaped dose-dependent manner and rescued the NaFAC-induced impairment of memory retrieval, suggesting links between LTD and spatial memory retrieval. Our study thus provides direct evidence of the bell-shaped D-serine actions on hippocampal LTD and spatial memory retrieval, and underscores the importance of D-serine in synaptic plasticity, learning, and memory.     

Synaptic influence of hippocampus on pyramidal cells of the rat prefrontal cortex: an in vivo intracellular recording study

The hippocampus and prefrontal cortex are two structures implicated in learning and memory and are related through a direct excitatory pathway. The characteristics of the synaptic influence of the hippocampus on pyramidal cells of the prefrontal cortex were determined using intracellular recordings in anesthetized rats. Single-pulse stimulation of the hippocampus induced an early EPSP of fixed latency in most of the recorded pyramidal cells (n = 106/116) thereby demonstrating a monosynaptic connection between hippocampal neurons and pyramidal cells of the prefrontal cortex. Furthermore, the EPSP was followed by a prolonged IPSP and suggests a simultaneous engagement of pyramidal and non-pyramidal neurons that may ultimately constrain the spread of excitation in response to hippocampal input. Paired-pulse stimulation induced short-term modifications in the synaptic responses and this short-term plasticity may contribute to the temporal filtering of information. Finally, tetanic stimulation of the hippocampus produced long-term potentiation of the monosynaptic EPSP with a concomitant potentiation of the IPSP, indicating that the hippocampo-prefrontal network can participate in the formation and consolidation of memories. In conclusion, the characteristics of the synaptic transmission in the hippocampo-prefrontal cortex pathway further supports the existence of a cooperative relationship between two structures known to be involved in higher cognitive processes.     

Study on cognition disorder and morphologic change of neurons in hippocampus area following traumatic brain injury in rats

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孕期吸入异氟醚对子代大鼠海马神经元突触可塑性的影响

目的 探讨孕期吸入异氟醚对子代大鼠海马神经元突触可塑性的影响.方法 孕14 d的SD大鼠10只,体重220～250 g,采用随机数字表法,将孕鼠随机分为对照组和异氟醚组,每组5只.对照组大鼠每天单纯机械通气2 h,异氟醚组大鼠每天吸入1.3%异氟醚2 h,至大鼠分娩.子代大鼠出生后4周,采用Morris水迷宫实验测定认知功能,测定结束后处死子代大鼠取脑,分离海马,采用透射电镜观察海马CA1区神经元突触的超微结构,计数海马神经元突触数量,测定突触后致密物质厚度.结果 与对照组相比,异氟醚组子代大鼠逃避潜伏期延长,穿越平台次数减少,海马神经元突触数量减少,突触后致密物质厚度降低(P<0.05).结论 孕期吸入异氟醚可通过抑制子代大鼠海马神经元突触的可塑性而降低其认知功能.

Abstract：

Objective To investigate the effect of isoflurane inhalation during gestation period on plasticity of hippo-campal synapses in offspring rats. Methods Ten healthy pregnant SD rats at 14 day gestation were randomly divided into 2 gorups ( n = 5 each): control group (group C) and isoflurane group (group I). The rats in group C were mechanically ventilated with O2 while in group I the rats inhaled 1.3% isoflurane in O2 for 2 h a day until labor. Four weeks after birth 4 offspring rats from each pregnant rats (2 male, 2 female) were tested for learning and memory abilities using Morris water maze. Then the offspring rats were sacrificed and hippocampi isolated. The synaptic structure of hippocampal CA1 area was examined by trans-electron microscopy. Results Morris water maze test showed that the escape latency was significantly shorter and the number of times of spanning flat roof greater in group C than in group I. The structure of hippocampus was intact in group C but incomplete in group I. Meanwhile the thickness of synaptic density was significantly decreased in group I. Conclusion Isoflurane anesthesia of pregnant rats may induce learning and memory disabilities in offspring rats by inhibiting the plasticity of synaptic structure in hippocampus.     

慢性疼痛对新生大鼠海马形态结构和学习记忆功能的影响

目的 探讨慢性疼痛刺激对新生大鼠海马形态结构和学习记忆功能的影响。方法60只出生7 d SD大鼠,随机化区组实验设计,每天予以疼痛组(n=30)新生大鼠后脚掌注射0.5％福尔马林0.1 ml,连续两周至哺乳期结束;对照组(n=30)新生大鼠后脚掌则用棉签予以接触刺激。两周后用Morris水迷宫试验检测大鼠空间学习记忆功能的情况;水迷宫试验完成后,取两组大鼠海马组织,作病理切片,对海马齿状回颗粒细胞、CA3区锥体细胞进行计数,对海马CA3区锥体细胞超微结构进行观测。结果在Morris水迷宫试验中,疼痛组潜伏期明显长于对照组(P<0.01);与疼痛组比较,对照组海马齿状回单位面积的颗粒细胞数目、CA3区单位面积的锥体细胞数目显著性升高(P<0.01);对照组海马CA3区锥体细胞线粒体形态正常、线粒体嵴清晰可见,胞浆内粗面内质网丰富、清晰可见。疼痛组海马CA3区锥体细胞体积缩小,线粒体嵴及粗面内质网减少。结论 长期慢性疼痛刺激可抑制新生大鼠空间学习记忆功能的发育,可抑制新生大鼠海马齿状回颗粒细胞的发育,并引起海马CA3区锥体细胞丢失。     

孕期吸入异氟醚对子代大鼠海马神经元突触可塑性的影响

目的 探讨孕期吸入异氟醚对子代大鼠海马神经元突触可塑性的影响.方法 孕14 d的SD大鼠10只,体重220～250 g,采用随机数字表法,将孕鼠随机分为对照组和异氟醚组,每组5只.对照组大鼠每天单纯机械通气2 h,异氟醚组大鼠每天吸入1.3%异氟醚2 h,至大鼠分娩.子代大鼠出生后4周,采用Morris水迷宫实验测定认知功能,测定结束后处死子代大鼠取脑,分离海马,采用透射电镜观察海马CA1区神经元突触的超微结构,计数海马神经元突触数量,测定突触后致密物质厚度.结果 与对照组相比,异氟醚组子代大鼠逃避潜伏期延长,穿越平台次数减少,海马神经元突触数量减少,突触后致密物质厚度降低(P<0.05).结论 孕期吸入异氟醚可通过抑制子代大鼠海马神经元突触的可塑性而降低其认知功能.     

孕期吸入异氟醚对子代大鼠海马神经元突触可塑性的影响

目的 探讨孕期吸入异氟醚对子代大鼠海马神经元突触可塑性的影响.方法 孕14 d的SD大鼠10只,体重220～250 g,采用随机数字表法,将孕鼠随机分为对照组和异氟醚组,每组5只.对照组大鼠每天单纯机械通气2 h,异氟醚组大鼠每天吸入1.3%异氟醚2 h,至大鼠分娩.子代大鼠出生后4周,采用Morris水迷宫实验测定认知功能,测定结束后处死子代大鼠取脑,分离海马,采用透射电镜观察海马CA1区神经元突触的超微结构,计数海马神经元突触数量,测定突触后致密物质厚度.结果 与对照组相比,异氟醚组子代大鼠逃避潜伏期延长,穿越平台次数减少,海马神经元突触数量减少,突触后致密物质厚度降低(P<0.05).结论 孕期吸入异氟醚可通过抑制子代大鼠海马神经元突触的可塑性而降低其认知功能.     

Fosphenytoin Reduces Hippocampal Neuronal Damage in Rat Following Transient Global Ischemia

Summary Fosphenytoin, a water-soluble disodium phosphate ester of phenytoin, is a phenytoin prodrug with similar anticonvulsant properties. In this study, we evaluated its neuroprotective properties in a cardiac arrest-induced global ischemia model. After 12 minute ischemia, Long-Evans hooded rats were resuscitated, given fosphenytoin (30 mg/kg, i.m.) or saline 5 minutes after the ischemic episode, and killed on day 7. Brains were removed, fixed, and vibratome sectioned to assess the numbers of normal appearing CAI pyramidal neurons and for immunohistological staining of glial fibrillary acidic protein (GFAP). After global ischemia, the number of hippocampal CA1 pyramidal neurons decreased significantly (from 14.33±1.73 to 2.19±0.16 per 100 μm²). Most hippocampal CA1 pyramidal neurons showed signs of injury and GFAP immunoreactivity of the region increased. With fosphenytoin treatment 5 min after ischemia, hippocampal CA1 pyramidal neurons remained at near control level (13.90±0.92), however, GFAP staining was not significantly changed. Our data, although indicating different neuronal and glial responses following fosphenytoin treatment, nevertheless, suggest that fosphenytoin is an effective neuroprotectant against ischemia-induced damage.     

Involvement of the mGluR1 receptor in hippocampal synaptic plasticity and associative learning in behaving mice

Metabotropic glutamate receptor 1 (mGluR1) has been related to processes underlying learning in hippocampal circuits, but demonstrating its involvement in synaptic plasticity when measured directly on the relevant circuit of a learning animal has proved to be technically difficult. We have recorded the functional changes taking place at the hippocampal CA3-CA1 synapse during the acquisition of an associative task in conscious mice carrying a targeted disruption of the mGluR1 gene. Animals were classically conditioned to evoke eyelid responses, using a trace (conditioned stimulus [CS], tone; unconditioned stimulus [US], electric shock) paradigm. Acquisition of this task was impaired in mutant mGluR1(+/-) mice and abolished in mGluR1(-/-) mice. A single pulse presented to Schaffer collaterals during the CS-US interval evoked a monosynaptic field excitatory postsynaptic potential at ipsilateral CA1 pyramidal cells, whose slope was linearly related to learning evolution in controls but not in mGluR1 mutants. Long-term potentiation evoked by train stimulation of Schaffer collaterals was also impaired in both mGluR1(+/-) and mGluR1(-/-) animals. Administration of the selective mGluR1 antagonist (3aS,6aS)-6a-naphthalen-2-ylmethyl-5-methyliden-hexahydro-cyclopental [c]furan-1-on to wild-type animals mimicked the functional changes associated to mGluR1 insufficiency in mutants. Thus, mGluR1 is required for activity-dependent synaptic plasticity and associative learning in behaving mice.     

Altered synaptic transmission in the hippocampus of the castrated male mouse is reversed by testosterone replacement

PURPOSE: To determine the effect of castration on hippocampal function, we have investigated synaptic transmission in the castrated male mouse in vivo. We also examined whether administering testosterone can reverse the changes. MATERIALS AND METHODS: Male 12 weeks-old C57BL/6J mice were divided into three experimental groups; sham-castration (Control), the castration group (Cast), and the castration plus testosterone propionate group (Cast+TP). Field excitatory postsynaptic potentials (fEPSP) were evoked in the CA1 area of the hippocampus by stimulating the commissural fibers of the contralateral hippocampus. Field EPSPs were evoked in the granular cells of the dentate gyrus (DG) by stimulating the ipsilateral perforant path fibers. RESULTS: Laminar analysis of the fEPSPs in the hippocampal CA1 pyramidal cell layer did not differ significantly between the three experimental groups. However, paired pulse facilitation (PPF) of the fEPSP with short inter-stimulus intervals (30 to 100 msec) was significantly suppressed in Cast group. This suppression was reversed by testosterone injection (Cast+TP). Longterm potentiation (LTP) in the CA1 pyramidal neurons by high frequency stimulation (HFS) did not differ significantly between the three experimental groups, whereas potentiation evoked by primed burst stimulation (PBS) was much weaker in the Cast group compared with the Control group. Testosterone injection restored the PBS-induced potentiation to the control level. Synaptic transmission between perforant pathway and the granule cells in the dentate gyrus (DG) did not differ significantly among the three experimental groups. CONCLUSIONS: Suppression of PPF and impairment of the potentiation by PBS in CA1 hippocampal neurons was observed in castrated male mice and these changes were reversed by testosterone injection. These findings suggest that altered synaptic transmission in the castrated male mouse is caused by disturbance of inhibitory neuronal networks that are influenced by testosterone.     

Homeostatic synaptic plasticity can explain post-traumatic epileptogenesis in chronically isolated neocortex

Chronically isolated neocortex develops chronic hyperexcitability and focal epileptogenesis in a period of days to weeks. The mechanisms operating in this model of post-traumatic epileptogenesis are not well understood. We hypothesized that the spontaneous burst discharges recorded in chronically isolated neocortex result from homeostatic plasticity (a mechanism generally assumed to stabilize neuronal activity) induced by low neuronal activity after deafferentation. To test this hypothesis we constructed computer models of neocortex incorporating a biologically based homeostatic plasticity rule that operates to maintain firing rates. After deafferentation, homeostatic upregulation of excitatory synapses on pyramidal cells, either with or without concurrent downregulation of inhibitory synapses or upregulation of intrinsic excitability, initiated slowly repeating burst discharges that closely resembled the epileptiform burst discharges recorded in chronically isolated neocortex. These burst discharges lasted a few hundred ms, propagated at 1-3 cm/s and consisted of large (10-15 mV) intracellular depolarizations topped by a small number of action potentials. Our results support a role for homeostatic synaptic plasticity as a novel mechanism of post-traumatic epileptogenesis.     

Reorganization of inhibitory synapses and increased PSD length of perforated excitatory synapses in hippocampal area CA1 of dystrophin-deficient mdx mice

Dystrophin is a cytoskeletal membrane-bound protein expressed in both muscle and brain. Brain dystrophin is thought to be involved in the stabilization of gamma-aminobutyric acid (GABA)(A)-receptor (GABA(A)-R)clusters in postsynaptic densities (PSDs) at inhibitory synapses onto pyramidal cells, and its loss has been linked to cognitive impairments in Duchenne muscular dystrophy. Dystrophin-deficient mdx mice have learning deficits and altered synaptic plasticity in cornu ammonis (CA1) hippocampus, but the possibility that altered synapse morphology or distribution may underlie these alterations has not been examined. Here we used in vivo magnetic resonance imaging and histological analyses to assess brain volumetric and cytoarchitectonic abnormalities and quantitative electron microscopy to evaluate the density and ultrastructure of CA1 hippocampal synapses in mdx mice. We found that mdx mice have increased density of axodendritic symmetric inhibitory synapses and larger PSDs in perforated asymmetric excitatory synapses in the proximal, but not distal, CA1 apical dendrites that normally express dystrophin, in the absence of gross brain malformations. Data are discussed in light of the known molecular and neurophysiological alterations in mdx mice. We suggest that increased inhibitory synapse density reflects tenuous compensation of altered clustering of alpha2 subunit-containing GABA(A)-Rs in CA1 dendrites, whereas increased PSD length in perforated synapses suggests secondary alterations in excitatory synapse organization associated with enhanced synaptic excitation.     

Functional expression of nicotinic acetylcholine receptors in rat neocortical layer 5 pyramidal cells

Neuronal nicotinic acetylcholine receptors (nAChRs) expressed by neurons of the neocortex are known to play a role in higher brain functions. Electrophysiological studies of neocortical neurons provided evidence that functional nAChRs are present on the axonal presynaptic terminals, on the somata and on dendrites of gamma-aminobutyric acid (GABA)ergic inhibitory interneurons. However, it is not clear if pyramidal neurons express functional postsynaptic nAChRs. Therefore, we investigated the action of locally applied acetylcholine (ACh) on layer 5 pyramidal neurons in the rat neocortex in vitro. In the presence of atropine, tetrodotoxin, glutamate receptor antagonists, and GABAA receptor antagonists, ACh induced membrane depolarizations which were generated by membrane inward currents consisting of a fast and a slow component. Analysis of the electrophysiological properties, the pharmacological characteristics, and the desensitization behavior of the 2 current components revealed that they were mediated by at least 2 different subtypes of the nAChR, most likely the alpha7-like and the alpha4beta2-like subtype. The expression of nAChRs in neocortical pyramidal cells raises the possibility that these neurons generate nicotinic excitatory postsynaptic potentials, thereby influencing cell excitability. Furthermore, because most nAChRs are permeable to calcium, they may modulate synaptic transmission and neuronal plasticity via a calcium-dependent postsynaptic mechanism.     

Passive spatial perception facilitates the expression of persistent hippocampal long-term depression

Learning-facilitated plasticity describes the ability of hippocampal synapses to respond with synaptic plasticity when weak afferent stimulation is coupled with a spatial learning event. Qualitative differences appear to influence whether long-term potentiation or long-term depression (LTD) are facilitated by spatial learning. At many hippocampal synapses, LTD is facilitated when rats actively explore a novel spatial context. We investigated whether learning-facilitated plasticity is expressed when an unconstrained but stationary rat observes a computer-generated spatial environment. Visual fields were separated. Novel object configurations were presented to one field; familiar constellations were presented to the other field. LTD was facilitated in the CA1 region of the hemisphere to which novel object constellations were presented. Familiar constellations had no effect. LTD facilitation was prevented by treatment with the protein translation inhibitor, anisomycin. LTD in the dentate gyrus was not facilitated by novel object constellations, suggesting that effects are not common to all hippocampal subfields. These data support a unique association of LTD in the CA1 region with learning about spatial context and indicate that rats can passively perceive space.