Spatial memory formation is enabled through synaptic information processing, in the form of persistent strengthening and weakening of synapses, within the hippocampus. It is, however, unclear how relevant spatial information is selected for encoding, in preference to less pertinent information. As the noradrenergic locus coeruleus (LC) becomes active in response to novel experiences, we hypothesized that the LC may provide the saliency signal required to promote hippocampal encoding of relevant information through changes in synaptic strength. Test pulse stimulation evoked stable basal synaptic transmission at Schaffer collateral (SC)–CA1 stratum radiatum synapses in freely behaving adult rats. Coupling of these test pulses with electrical stimulation of the LC induced long-term depression (LTD) at SC–CA1 synapses and induced a transient suppression of theta-frequency oscillations. Effects were N-methyl-D-aspartate and β-adrenergic receptor dependent. Activation of the LC also increased CA1 noradrenalin levels and facilitated the encoding of spatial memory for a single episode via a β-adrenoceptor–dependent mechanism. Our results demonstrate that the LC plays a key role in the induction of hippocampal LTD and in promoting the encoding of spatial information. This LC–hippocampal interaction may reflect a means by which salient information is distinguished for subsequent synaptic processing.

Modified cortical excitability following repetitive transcranial magnetic stimulation (rTMS) may be related to short- or long-term synaptic plasticity of neuronal excitation but could also affect cortical inhibition. Therefore, in the rat we tested how three different rTMS protocols, intermittent and continuous theta-burst (iTBS, cTBS), and low-frequency 1 Hz stimulation, change the expression of GAD65, GAD67 and GAT-1 which are expressed in cortical inhibitory interneurons in an activity-dependent manner. Acutely (2 h), all protocols reduced the expression of GAD67 in frontal, motor, somatosensory and visual cortex but increased that of GAD65 and GAT-1 to different degree, with iTBS having the strongest acute effect. The initial decrease in GAD67 reversed after 1 day, leading to a strong increase in GAD67 expression for up to 7 days primarily in the frontal cortex in case of iTBS, cTBS and in all studied areas following 1 Hz rTMS. While also GAD65 and GAT-1 expression reversed after 1 day in case of iTBS and cTBS, 1 Hz rTMS induced a steady increase in GAD65 and GAT-1 expression during the 7 days investigated. Our data demonstrate that rTMS affects the expression of activity-dependent proteins of the cortical inhibitory interneurons. Besides common effects of low- (1 Hz) and high-frequency (TBS) stimulation on protein expression, differences in quantity and time course of changes point to differences in the contribution of possible neuronal subsystems. Further studies are needed to distinguish cell-type specific effects.

Repetitive transcranial magnetic stimulation (rTMS) has been shown to alter cortical excitability depending on the stimulus-frequency used, with high frequency (5 Hz and higher) increasing it but low frequency (usually 1 Hz or lower) reducing it. To determine the efficiency of different rTMS protocols in inducing cortical network activity, we tested the acute effect of one low-frequency rTMS protocol (1 Hz) and two different high-frequency protocols (10 Hz and intermittent theta-burst stimulation, iTBS) on the expression of the two immediate early gene (IEG) proteins c-Fos and zif268 in the rat brain. The cortical expression of both IEGs was specifically changed in an rTMS-dependent manner. One and 10 Hz rTMS enhanced c-Fos protein expression in all cortical areas tested, while iTBS was effective only in limbic cortices. Zif268 expression was increased in almost all cortical areas after iTBS, while 10 Hz rTMS was effective only in the primary motor and sensory cortices. One Hertz rTMS had no effect on cortical zif268 expression. Furthermore, sham-rTMS had no effect on zif268 expression but increased c-Fos in limbic cortices. This is the first study demonstrating that cortical zif268 and c-Fos expression can be specifically modulated by acute rTMS depending on the pattern of stimulation applied.

Repetitive transcranial magnetic stimulation (rTMS) has been shown to alter cortical excitability that lasts beyond the duration of rTMS application itself. High-frequency rTMS leads primarily to facilitation, whereas low-frequency rTMS leads to inhibition of the treated cortex. However, the contribution of rTMS train duration is less clear. In this study, we investigated the effects of nine different rTMS protocols, including low and high frequencies, as well as short and long applications (1, 3 and 10 Hz applied for 1, 5 and 20 min), on visual cortex excitability in anaesthetized and paralysed cats by means of visual evoked potential (VEP) and electroencephalography (EEG) recordings. Our results show that 10 Hz rTMS applied for 1 and 5 min significantly enhanced early VEP amplitudes, while 1 and 3 Hz rTMS applied for 5 and 20 min significantly reduced them. No significant changes were found after 1 and 3 Hz rTMS applied for only 1 min, and 10 Hz rTMS applied for 20 min. EEG activity was only transiently (<20 s) affected, with increased delta activity after 1 and 3 Hz rTMS applied for 1 or 5 min. These findings indicate that the effects of rTMS on cortical excitability depend on the combination of stimulus frequency and duration (or total number of stimuli): short high-frequency trains seem to be more effective than longer trains, and low-frequency rTMS requires longer applications. Changes in the spectral composition of the EEG were not correlated to changes in VEP size. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive and largely painless technique to stimulate the human brain. It is preferentially applied to cortical areas with the intention to either disturb ongoing processing in the targeted area (virtual lesion) or to modulate the general excitability of the cortical network. Besides transient effects, numerous studies have shown that rTMS has modulatory effects on cortical excitability that last for seconds to many minutes beyond the duration of the rTMS application itself. The primary motor cortex has been used extensively for rTMS studies because the effects of stimulation are easy to quantify by measuring the size of motor-evoked potentials (MEPs). Findings to date suggest that the modulatory effects of rTMS on cortical excitability may be inhibitory or facilitatory depending on the frequency, intensity and duration of the stimulus (see Modugno et al. 2001). A few examples: high-frequency rTMS, especially at high stimulus intensities, leads to facilitation of corticospinal activity; a 10-pulse rTMS train of 20 Hz applied at a strength of 150% resting motor threshold (RMT) caused an increase in MEP size lasting for about 3 min (Pascual-Leone et al. 1994); a 30-pulse rTMS train at 120% RMT and 15 Hz caused a shorter and smaller increase in MEP size for only 90 s (Wu et al. 2000). Stimulation intensities below RMT usually require longer trains before any lasting effect is seen. Maeda et al. (2000a,b) reported a facilitation of MEPs for 2 min after administration of 240 pulses of 20 ...

In this study we aimed to investigate whether reduced BDNF levels aggravate the susceptibility of the brain to hazardous effects of high fat diet. For this purpose, we fed BDNF heterozygous mice and wild type littermates with normal and high fat diet for 16 weeks. Concentrations of two synaptic proteins (SNAP-25 and PSD-95) and oxidative stress parameters (MDA, SOD, CAT) were evaluated in the cortex after diet period. Interestingly, body weights of BDNF heterozygous groups fed with control diet were higher than their littermates and heterozygous mice fed with HFD were the heaviest in all experimental groups. MDA levels were significantly elevated in both HFD groups (wild type and BDNF(+/-)). Synaptic markers PSD-95 and SNAP-25 markedly decreased in BDNF(+/-) group fed with HFD compared to other groups. In conclusion, we suggest that endogenous BDNF has an important and possibly protective role in diet-induced changes in the cortex.