Primed-burst potentiation in adult rat visual cortex in vitro

The effectiveness of θ pattern primed-bursts (PBs) on development of PB potentiation was investigated in layer II/III of the adult rat visual cortex in vitro. Experiments were carried out in the visual cortical slices. Population excitatory postsynaptic potentials (pEPSPs) were evoked in layer II/III by stimulation of either white matter or layer IV. To induce long-term potentiation (LTP), eight episodes of PBs were delivered at 0.1 Hz. Regardless of stimulation site, field potential recorded in layer II/III consisted of two components: a short latency and high amplitude response called pEPSP1, and a long latency and low amplitude response called pEPSP2. The incidence of LTP produced by PBs of layer IV was higher than that of the white matter tetanization. In contrast, PBs of both layer IV and white matter reliably produced LTP of pEPSP2 in layer II/III. It is concluded that PBs, as a type of activity pattern, of either white matter or layer IV can gain access to the modifiable synapses that are related to pEPSP2 in layer II/III, but accessibility of the modifiable synapses that are related to pEPSP1 depends on tetanization site. Relevancy of the results to the plasticity gate hypothesis is also discussed.     

Visual deprivation increases capability of layer II/III for epileptiform activity in the rat visual cortical slices

Effects of visual deprivation on the induction of epileptiform activity were studied in layer II/III of 29-39-day-old rat primary visual cortex. Field potentials were evoked by stimulation of layer IV in slices from control (CON) and dark-reared (DR) rats. Picrotoxin (PTX)-induced epileptiform activity was characterized by spontaneous and evoked epileptic field potentials (EFPs). The results showed that DR slices demonstrate greater susceptibility for induction of spontaneous EFP. PTX-induced changes in the characteristics of evoked field potentials also showed higher tendency of DR animals to generate epileptiform activity. In both groups, field potentials consisted of pEPSP(1) (population excitatory postsynaptic potential 1, i.e., first negativity) and pEPSP(2) (second negativity), respectively. There was no significant difference between the characteristics of field potentials in CON and DR slices. PTX significantly increased amplitude and duration of pEPSP(2), but it had no significant effect on pEPSP(1). Effects of PTX on pEPSP(2) were significantly higher in DR slices. It is concluded that visual deprivation results in a heightened potential in layer II/III of the rat visual cortex to generate PTX-induced epileptiform activity.     

Differential effects of pentylenetetrazol-kindling on long-term potentiation of population excitatory postsynaptic potentials and population spikes in the CA1 region of rat hippocampus

The effects of pentylenetetrazol-kindling on synaptic transmission and the effectiveness of θ pattern primed-bursts (PBs) for the induction of long-term potentiation (LTP) of population excitatory postsynaptic potentials and population spikes were investigated in hippocampal CA1 of pentylenetetrazol-kindled rats. Experiments were carried out in the control and kindled animals at two post-kindling periods, i.e., 48-144 h (early phase) and 30-33 days (long lasting phase). Field potentials (population excitatory postsynaptic potentials, pEPSPs; and population spikes, PSs) were recorded at the stratum radiatum and the stratum pyramidale following stimulation of the stratum fibers, respectively. PBs were delivered to stratum fibers and PB potentiation was assessed. The results showed that 48-144 h after kindling there was no significant difference for pEPSP slope and PS amplitude between two groups. But at 30-33 days after kindling, the pEPSP slope in the stratum radiatum of kindled animals decreased, whereas the amplitude of PSs increased compared to those of controls. Shortly after kindling, control animals had normal LTP of pEPSP slope and PS amplitude in response to PBs, but kindled rats lack LTP of pEPSP slope and PBs induced LTP of PS amplitude in most of kindled animals. In 30-33 days after kindling, PB potentiation was not observed in the stratum radiatum of kindled animals but PBs induced LTP of PS amplitude, which was significantly greater than that of control animals. The effect is compatible with the hypothesis, which postulates kindling-associated functional deficit in hippocampus, especially CA1, as an explanation for the behavioral deficits seen with the kindling model of epilepsy.     

Long-term depression but not potentiation is induced in Ca(2+)-chelated visual cortex neurons

An entry of Ca2+ into postsynaptic sites may play a role in the induction of long-term potentiation (LTP) of synaptic transmission in the visual cortex. To test this hypothesis, a Ca(2+)-chelator was injected into layer II/III neurons of sliced visual cortex obtained from young rats, and excitatory postsynaptic potentials (EPSPs) of these cells to test stimulation of the white matter were observed before and after tetanic stimulation of the same site. To confirm the effectiveness of the tetanus, field potentials reflecting the activities of many cells were recorded with another extracellular electrode. The chelator injection led to long-term depression (LTD) of EPSPs following tetanic stimuli which simultaneously induced LTP of field potentials derived from unchelated cells in most of the slices tested. This suggests that a low concentration of post-synaptic, free Ca2+, when associated with tetanic inputs, may lead to LTD while a rise of Ca2+ may lead to LTP.     

Calcium Channel-Dependent Induction of Long-Term Synaptic Plasticity at Excitatory Golgi Cell Synapses of Cerebellum

Golgi cells, together with granule cells and mossy fibers, form a neuronal microcircuit regulating information transfer at the cerebellum input stage. Despite theoretical predictions, little was known about long-term synaptic plasticity at Golgi cell synapses. Here, we have used whole-cell patch-clamp recordings and calcium imaging to investigate long-term synaptic plasticity at excitatory synapses impinging on Golgi cells. In acute mouse cerebellar slices, mossy fiber theta-burst stimulation (TBS) could induce either long-term potentiation (LTP) or long-term depression (LTD) at mossy fiber-Golgi cell and granule cell-Golgi cell synapses. This synaptic plasticity showed a peculiar voltage dependence, with LTD or LTP being favored when TBS induction occurred at depolarized or hyperpolarized potentials, respectively. LTP required, in addition to NMDA channels, activation of T-type Ca²⁺ channels, while LTD required uniquely activation of L-type Ca²⁺ channels. Notably, the voltage dependence of plasticity at the mossy fiber-Golgi cell synapses was inverted with respect to pure NMDA receptor-dependent plasticity at the neighboring mossy fiber-granule cell synapse, implying that the mossy fiber presynaptic terminal can activate different induction mechanisms depending on the target cell. In aggregate, this result shows that Golgi cells show cell-specific forms of long-term plasticity at their excitatory synapses, that could play a crucial role in sculpting the response patterns of the cerebellar granular layer.SIGNIFICANCE STATEMENT This article shows for the first time a novel form of Ca²⁺ channel-dependent synaptic plasticity at the excitatory synapses impinging on cerebellar Golgi cells. This plasticity is bidirectional and inverted with respect to NMDA receptor-dependent paradigms, with long-term depression (LTD) and long-term potentiation (LTP) being favored at depolarized and hyperpolarized potentials, respectively. Furthermore, LTP and LTD induction requires differential involvement of T-type and L-type voltage-gated Ca²⁺ channels rather than the NMDA receptors alone. These results, along with recent computational predictions, support the idea that Golgi cell plasticity could play a crucial role in controlling information flow through the granular layer along with cerebellar learning and memory.     

Reduced presynaptic efficiency of excitatory synaptic transmission impairs LTP in the visual cortex of BDNF-heterozygous mice

The neurotrophin brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival, axonal and dendritic growth and synapse formation. BDNF has also been reported to mediate visual cortex plasticity. Here we studied the cellular mechanisms of BDNF-mediated changes in synaptic plasticity, excitatory synaptic transmission and long-term potentiation (LTP) in the visual cortex of heterozygous BDNF-knockout mice (BDNF(+/-)). Patch-clamp recordings in slices showed an approximately 50% reduction in the frequency of miniature excitatory postsynaptic currents (mEPSCs) compared to wild-type animals, in the absence of changes in mEPSC amplitudes. A presynaptic impairment of excitatory synapses from BDNF(+/-) mice was further indicated by decreased paired-pulse ratio and faster synaptic fatigue upon prolonged repetitive stimulation at 40 Hz. In accordance, presynaptic theta-burst stimulation (TBS) failed to induce LTP at layer IV to layers II-III synapses during extracellular field-potential recordings in BDNF(+/-) animals. Changes in postsynaptic function could not be detected, as no changes were observed in either the amplitudes of evoked EPSCs, the ratios of AMPA : NMDA currents or the kinetics of evoked AMPA and NMDA EPSCs. In line with this observation, an LTP pairing paradigm that relies on direct postsynaptic depolarization under patch-clamp conditions could be induced successfully in BDNF(+/-) animals. These data suggest that a chronic reduction in the expression of BDNF to nearly 50% attenuates the efficiency of presynaptic glutamate release in response to repetitive stimulation, thereby impairing presynaptically evoked LTP in the visual cortex.     

Metabotropic glutamate receptors mediate expression of LTP in slices of rat visual cortex

Long-term-potentiation (LTP) can be induced by application of a standard theta-burst stimulation protocol in slice preparations of the neocortex. This type of LTP is known to be dependent on the activation of NMDA receptors. The present study used specific experimental conditions to evoke a non-NMDA receptor mediated type of LTP. By use of weak theta-burst stimulation (wTBS) we describe a non-NMDA receptor dependent LTP in rat visual cortex in vitro, which is sensitive to an antagonist of metabotropic glutamate receptors (mGluR). In slices of the visual cortex we stimulated ascending inputs in cortical layer IV and recorded extracellular field potentials (FPs) from cortical layers II/III. In disinhibited slices (with 1 microm picrotoxin), a wTBS induced LTP to 138% of control. The expression of this potentiation was insensitive to the NMDA-receptor antagonist, D-AP5, but could be abolished by application of the mGluR antagonist MCPG. These data suggest an NMDA-independent mechanism for LTP induction in the visual cortex which can be observed in layer II/III neurons.     

Environmental enrichment potentiates thalamocortical transmission and plasticity in the adult rat visual cortex

It has been demonstrated that the complex sensorimotor and social stimulation achieved by rearing animals in an enriched environment (EE) can reinstate juvenile‐like plasticity in the adult cortex. However, it is not known whether EE can affect thalamocortical transmission. Here, we recorded in vivo field potentials from the visual cortex evoked by electrical stimulation of the dorsal lateral geniculate nucleus (dLGN) in anesthetized rats. We found that a period of EE during adulthood shifted the input–output curves and increased paired‐pulse depression, suggesting an enhanced synaptic strength at thalamocortical terminals. Accordingly, EE animals showed an increased expression of the vesicular glutamate transporter 2 (vGluT‐2) in geniculocortical afferents to layer IV. Rats reared in EE also showed an enhancement of thalamocortical long‐term potentiation (LTP) triggered by theta‐burst stimulation (TBS) of the dLGN. To monitor the functional consequences of increased LTP in EE rats, we recorded visual evoked potentials (VEPs) before and after application of TBS to the geniculocortical pathway. We found that responses to visual stimulation were enhanced across a range of contrasts in EE animals. This was accompanied by an up‐regulation of the intracortical excitatory synaptic marker vGluT‐1 and a decrease in the expression of the vesicular GABA transporter (vGAT), indicating a shift in the excitation/inhibition ratio. Thus, in the adult rat, EE enhances synaptic strength and plasticity of the thalamocortical pathway associated with specific changes in glutamatergic and GABAergic neurotransmission. These data provide novel insights into the mechanisms by which EE shapes the adult brain. © 2010 Wiley‐Liss, Inc.     

Reduced long-term potentiation in hippocampal slices prepared using sucrose-based artificial cerebrospinal fluid

Sucrose-based artificial cerebrospinal fluid (aCSF) is sometimes used to prepare brain slices for in vitro electrophysiological experiments. This study compared the effect of preparing brain slices using chilled sucrose-based aCSF versus the conventional method using chilled aCSF on hippocampal synaptic plasticity. Brain slices from each treatment group were transferred to normal aCSF before electrophysiological recordings were made. The stimulus–response relationship of field excitatory postsynaptic potentials (fEPSPs) in the CA1 region was indistinguishable between the two treatment groups. However, the amount of LTP induced by either a θ-burst (four stimuli at 100 Hz repeated ten times at 200 ms intervals) or tetanic stimulation (100 Hz for 1 s) was significantly reduced in slices that had been prepared using sucrose-based aCSF. This was associated with reduced facilitation of the fEPSPs during the high frequency stimulus, reduced post-tetanic potentiation and short-term potentiation. In sucrose-cut slices the fEPSPs were slightly shorter in duration (29%, P<0.01), and during paired-pulse stimulation the broadening of the second fEPSP was enhanced. The LTP deficit in sucrose-cut slices was reversed by blocking GABA_A receptor function with picrotoxin. These data suggest that the use of sucrose based aCSF better preserves GABA-mediated synaptic transmission, which limits the induction of LTP in hippocampal brain slices.     

Laminar distribution of cholinergic- and serotonergic-dependent plasticity within kitten visual cortex

Both cholinergic and serotonergic modulatory projections to mammalian striate cortex have been demonstrated to be involved in the regulation of postnatal plasticity, and a striking alteration in the number and intracortical distribution of cholinergic and serotonergic receptors takes place during the critical period for cortical plasticity. As well, agonists of cholinergic and serotonergic receptors have been demonstrated to facilitate induction of long-term synaptic plasticity in visual cortical slices supporting their involvement in the control of activity-dependent plasticity. We recorded field potentials from layers 4 and 2/3 in visual cortex slices of 60--80 day old kittens after white matter stimulation, before and after a period of high frequency stimulation (HFS), in the absence or presence of either cholinergic or serotonergic agonists. At these ages, the HFS protocol alone almost never induced long-term changes of synaptic plasticity in either layers 2/3 or 4. In layer 2/3, agonist stimulation of m1 receptors facilitated induction of long-term potentiation (LTP) with HFS stimulation, while the activation of serotonergic receptors had only a modest effect. By contrast, a strong serotonin-dependent LTP facilitation and insignificant muscarinic effects were observed after HFS within layer 4. The results show that receptor-dependent laminar stratification of synaptic modifiability occurs in the cortex at these ages. This plasticity may underly a control system gating the experience-dependent changes of synaptic organization within developing visual cortex.     

Input-specific induction of long-term depression in Ca(2+)-chelated visual cortex neurons

An input-dependent increase in postsynaptic Ca2+ may play a role in long-term potentiation (LTP) of synaptic transmission while no or subthreshold increase in Ca2+ is associated with long-term depression (LTD) in the developing visual cortex. To see whether LTD is induced only at tetanized synapses, a Ca(2+)-chelator was injected into layer 2/3 neurons in cortical slices from young rats, and excitatory postsynaptic potentials (EPSPs) of these cells, after test stimulation of the white matter and layer 1/2, were observed before and after tetanic stimulation of the former site. The chelator injection led to LTD of EPSPs at tetanized synapses, but no changes were seen at non-tetanized synapses. These results suggest that tetanic inputs induce LTD at tetanized synapses when they are associated with no or subtle increase in postsynaptic Ca2+.     

Involvement of T-type Ca2+ channels in the potentiation of synaptic and visual responses during the critical period in rat visual cortex

Neocortical neuronal circuits are refined by experience during the critical period of early postnatal life. The shift of ocular dominance in the visual cortex following monocular deprivation has been intensively studied to unravel the mechanisms underlying the experience-dependent modification. Synaptic plasticity is considered to be involved in this process. We previously showed in layer 2/3 pyramidal neurons of rat visual cortex that low-frequency stimulation-induced long-term potentiation (LTP) at excitatory synapses, which requires the activation of Ni²⁺-sensitive (R-type or T-type) voltage-gated Ca²⁺ channels (VGCCs) for induction, shared a similar age and experience dependence with ocular dominance plasticity. In this study, we examined whether this LTP is involved in ocular dominance plasticity. In visual cortical slices, LTP was blocked by mibefradil, kurtoxin and R -(−)-efonidipine, T-type VGCC blockers, but not by SNX-482, an R-type VGCC blocker, indicating that LTP induction requires T-type VGCC activation. Mibefradil did not affect synaptic transmission even at a dose about 30 times higher than that required for LTP blockade. Therefore, this drug was used to test the effect of T-type VGCC blockade on ocular dominance shift produced by 6 days of monocular deprivation during the critical period using visual evoked potentials (VEPs). Although this monocular deprivation commonly produced both depression of deprived eye responses and potentiation of nondeprived eye responses, only the former change occurred when mibefradil was infused into the visual cortex during monocular deprivation. Mibefradil infusion produced no acute effects on VEPs. These results suggest that T-type VGCC-dependent LTP contributes to the experience-dependent enhancement of visual responses.     

Endogenous somatostatin receptors mobilize calcium from inositol 1,4,5-trisphosphate-sensitive stores in NG108-15 cells

Injury and loss of neurons are observed in the center of a cerebral cortical lesion. Mechanisms of early functional reorganization post-lesion involve changes in the strength of synaptic coupling as measured in long-term potentiation (LTP). Since these changes in LTP may depend on the intraneuronal calcium concentration ([Ca²⁺]_I), the present study analyzed the strength of synaptic LTP combined with measurements of the stimulus-induced peak calcium influx in slices from rat visual cortex in vitro. Slices were analyzed 1–7 days post-lesion by use of electrophysiological and calcium fluorescence imaging techniques. A theta-burst stimulus (TBS) was electrically applied to cortical layer IV, while changes in extracellular field potentials (FPs) and in the corresponding peak calcium influx were recorded in layers II/III. Both the strength of LTP and of the FP mediated peak calcium influx were significantly enhanced 1–6 days post-lesion at a distance of 4 mm from the lesion border. Pharmacological experiments revealed that the expression of LTP was dependent on the activation of NMDA receptors. The area of increased stimulus-evoked peak calcium influx correlated with the enhanced LTP, suggesting that changes in [Ca²⁺]_I mediate the strength of long-term synaptic plasticity following a cortical lesion. This mechanism may support synaptic reorganization in the surround of the deafferented region in rat visual cortex.     

Coordination of size and number of excitatory and inhibitory synapses results in a balanced structural plasticity along mature hippocampal CA1 dendrites during LTP

Enlargement of dendritic spines and synapses correlates with enhanced synaptic strength during long‐term potentiation (LTP), especially in immature hippocampal neurons. Less clear is the nature of this structural synaptic plasticity on mature hippocampal neurons, and nothing is known about the structural plasticity of inhibitory synapses during LTP. Here the timing and extent of structural synaptic plasticity and changes in local protein synthesis evidenced by polyribosomes were systematically evaluated at both excitatory and inhibitory synapses on CA1 dendrites from mature rats following induction of LTP with theta‐burst stimulation (TBS). Recent work suggests dendritic segments can act as functional units of plasticity. To test whether structural synaptic plasticity is similarly coordinated, we reconstructed from serial section transmission electron microscopy all of the spines and synapses along representative dendritic segments receiving control stimulation or TBS‐LTP. At 5 min after TBS, polyribosomes were elevated in large spines suggesting an initial burst of local protein synthesis, and by 2 h only those spines with further enlarged synapses contained polyribosomes. Rapid induction of synaptogenesis was evidenced by an elevation in asymmetric shaft synapses and stubby spines at 5 min and more nonsynaptic filopodia at 30 min. By 2 h, the smallest synaptic spines were markedly reduced in number. This synapse loss was perfectly counterbalanced by enlargement of the remaining excitatory synapses such that the summed synaptic surface area per length of dendritic segment was constant across time and conditions. Remarkably, the inhibitory synapses showed a parallel synaptic plasticity, also demonstrating a decrease in number perfectly counterbalanced by an increase in synaptic surface area. Thus, TBS‐LTP triggered spinogenesis followed by loss of small excitatory and inhibitory synapses and a subsequent enlargement of the remaining synapses by 2 h. These data suggest that dendritic segments coordinate structural plasticity across multiple synapses and maintain a homeostatic balance of excitatory and inhibitory inputs through local protein‐synthesis and selective capture or redistribution of dendritic resources. ©2010 Wiley‐Liss, Inc.     

Long-term depression in horizontal slices of the rat lateral amygdala

Long-term depression (LTD) is an enduring decrease in synaptic efficacy and is thought to underlie memory. In contrast to investigations of plasticity mechanisms in the amygdala in rat coronal slices, this study was done in horizontal slices. Field excitatory postsynaptic potentials (fEPSPs) and EPSPs, respectively, were recorded extracellularly and intracellularly from the lateral nucleus of the amygdala (LA). We show that low-frequency stimulation (LFS) induces LTD in the LA, when stimulation electrodes were located in the LA. No significant differences were found between females and males. In dependence of strain variations, a reduction of GABAergic inhibition either reduced the magnitude of LTD or was a prerequisite for the induction of extracellularly recorded LA-LTD. Theta pulse stimulation (TPS) of afferents within the LA caused a weaker LTD than LFS. Theta burst stimulation (TBS) given 20 min after the end of LFS reversed LTD, whereas high-frequency stimulation (HFS) resulted in long-term potentiation (LTP) that was significantly stronger than that obtained in naive slices. Therefore, primed induction of LTD facilitates high-frequency-induced LTP in the rat lateral amygdala. NMDARs as well as group II mGluRs were involved in the mediation of LA-LTD. In contrast to data obtained by stimulation of afferents running within the LA, LFS of the external capsule fibers induced a weak LA-LTD, and TPS was not able to induce LTD. This study showed for the first time that LTD can be induced in the LA by standard LFS (900 pulses at 1 Hz) and that LTP stimuli reversed LTD. The results also provide further evidence for the broad sensitivity of synaptic plasticity mechanisms to the history of prior activity.     

The superoxide anion is involved in the induction of long-term potentiation in the rat somatosensory cortex in vitro

The involvement of the superoxide anion (O2-) in the induction of neocortical long-term potentiation (LTP) was examined in rat brain slices containing the primary somatosensory cortex. Field potentials evoked by stimulation in cortical layer IV were recorded from layer II/III. In control experiments, tetanic high-frequency stimulation (HFS) resulted in essentially input-specific, NMDA receptor-dependent LTP (20.2+/-3.0% increase in field potential amplitude). When the availability of intracellular O2- was reduced by application of the cell membrane-permeable O2- scavengers MnTBAP or CP-H (spin trap), HFS-induced LTP was attenuated to 12.0+/-1.7% and 8.7+/-3.1% increase, respectively. In contrast, HFS-induced LTP was not significantly affected by the cell membrane-impermeable O2- scavenger superoxide dismutase (SOD). Induction of the generation of O2- by the cell membrane-permeable redox-cycling quinone DMNQ resulted in a HFS-independent slow-onset LTP (21.8+/-6.0%) in three of eight brain slices. Together, these results suggest the contribution of O2- to the induction of LTP in the primary somatosensory cortex by an action on intracellular induction mechanisms.     

Endogenously released ACh and exogenous nicotine differentially facilitate long-term potentiation induction in the hippocampal CA1 region of mice

We examined the role of α7- and β2-containing nicotinic acetylcholine receptors (nAChRs) in the induction of long-term potentiation (LTP). Theta-burst stimulation (TBS), mimicking the brain's naturally occurring theta rhythm, induced robust LTP in hippocampal slices from α7 and β2 knockout mice. This suggests TBS is capable of inducing LTP without activation of α7- or β2-containing nAChRs. However, when weak TBS was applied, the modulatory effects of nicotinic receptors on LTP induction became visible. We showed that during weak TBS, activation of α7 nAChRs occurs by the release of ACh, contributing to LTP induction. Additionally, bath-application of nicotine activated β2-containing nAChRs to promote LTP induction. Despite predicted nicotine-induced desensitization, synaptically mediated activation of α7 nAChRs still occurs in the presence of nicotine and contributed to LTP induction. Optical recording of single-stimulation-evoked excitatory activity with a voltage-sensitive dye revealed enhanced excitatory activity in the presence of nicotine. This effect of nicotine was robust during high-frequency stimulation, and was accompanied by enhanced burst excitatory postsynaptic potentials. Nicotine-induced enhancement of excitatory activity was observed in slices from α7 knockout mice, but was absent in β2 knockout mice. These results suggest that the nicotine-induced enhancement of excitatory activity is mediated by β2-containing nAChRs, and is related to the nicotine-induced facilitation of LTP induction. Thus, our study demonstrates that the activation of α7- and β2-containing nAChRs differentially facilitates LTP induction via endogenously released ACh and exogenous nicotine, respectively, in the hippocampal CA1 region of mice.     

Impaired expression of long-term potentiation in hippocampal slices 4 and 48 h following mild fluid-percussion brain injury in vivo

The effect of fluid percussion brain injury on hippocampal long-term potentiation (LTP) was investigated in hippocampal slices in vitro. Mild to moderate (1.7–2.1 atm) lateral fluid percussion head injury or sham operation was produced in rats 4 or 48 h prior to harvesting brain slices from the ipsilateral hippocampus. Field excitatory post-synaptic potentials (fEPSPs) were recorded in stratum radiatum of hippocampal subfield CA1 in response to electrical stimulation of the Schaffer collaterals. The initial slope of fEPSPs was used to investigate changes in synaptic strength prior to and following 100 or 200 Hz (1 s) tetanic stimulation. TBI significantly inhibited expression of LTP in hippocampal slices in vitro. Post-tetanus fEPSP slopes increased more than 100% in hippocampal slices from sham-operated animals but less than 50% in slices from rats following TBI. The data suggest that changes in functional synaptic plasticity in the hippocampus may contribute to cognitive disorders associated with TBI (traumatic brain injury). The data also indicate that TBI-induced effects on hippocampal LTP are robust and may be investigated in the hippocampal slice preparation in vitro.     

Repeated administration of pentylenetetrazol alters susceptibility of rat hippocampus to primed-burst stimulation: evidence from in vitro study on CA1 of hippocampal slices

The effectiveness of θ pattern primed-bursts (PBs) on development of primed-burst (PB) potentiation was investigated in hippocampal CA1 of pentylenetetrazol-kindled rats. Experiments were carried out in the hippocampal slices from control and kindled rats at two post-kindling periods, i.e. 48–144 h (early phase) and 30–33 days (long-lasting phase). Field potentials (population excitatory post-synaptic potential, pEPSP) were recorded at stratum radiatum following stimulation of the stratum fibers. θ pattern primed-bursts were delivered to stratum radiatum and PB potentiation was assessed. The results showed that 48–144 h after kindling, PB potentiation in CA1 of kindled slices is significantly greater than control slices. In contrast, 30–33 days after kindling PB potentiation was not observed and the pEPSP slope was depressed after PBs delivery, which lasted at least 60 min. Our results suggest that shortly after kindling, PB potentiation can be more readily induced while one month later, it is more difficult to elicit. These findings may help to explain the behavioral deficits seen with the kindling model of epilepsy.     

Differential effects of long and short train theta burst stimulation on LTP induction in rat anterior cingulate cortex slices: Multi-electrode array recordings

Objective

There is substantial evidence supporting the notion that the anterior cingulate cortex (ACC) is an important limbic structure involved in multiple brain functions such as sensory perception, motor conflict monitoring, memory, emotion and cognition. It has been shown that long term potentiation (LTP) is an important synaptic model of neural plasticity in the ACC, however, little is known about the spatiotemporal properties of ACC at network level. The present study was designed to see the LTP induction effects across different layers of the ACC by using different conditioning stimuli (CS) protocols.

Methods

A unique multi-electrode array recording technique was used in the acutely-dissociated ACC slices of rats. Long and short train theta burst stimulation (TBS) paradigms were applied in layer V–VI as the CS and the LTP induction effects were compared across different layers of the ACC. Briefly, both long and short train TBS are composed of bursts (4 pulses at 100 Hz) with a 200 ms interval, however, the former (TBS1) was with 10 trains and the latter (TBS2) was with 5 trains. After test stimulation at layer V–VI in the ACC, network field potentials (FPs) could be simultaneously recorded across all layers of the ACC.

Results

The waveforms of FPs were different across different layers. Namely, positive-going waveforms were recorded in layer I and negative-going waveforms were recorded in layers V–VI, in contrast, complex waveforms were localized mainly in layers II–III. Following application of two CS protocols, the induction rate of LTP was significantly different between TBS1 and TBS2 regardless of the spatial properties. TBS1 had more than 60% success, while TBS2 was less than 25% in induction of LTP. Moreover, both the 2 CS protocols could induce LTP in layers II–III and layers V–VI without layer-related difference. However, no LTP was inducible in layer I.

Conclusion

The present findings indicate that stimulation protocols may, at least in part, account for a large portion of variations among previous LTP studies, and hence highlight the importance of selecting the best LTP induction protocol when designing such experiments. Moreover, the present results demonstrate the prominent superiority of multi-electrode array recording in revealing the network properties of synaptic activities in the ACC, especially in comparing the spatiotemporal characteristics between different layers of this structure.