Visual Cortex Plasticity Evokes Excitatory Alterations in the Hippocampus

The integration of episodic sequences in the hippocampus is believed to occur during theta rhythm episodes, when cortico-hippocampal dialog results in reconfiguration of neuronal assemblies. As the visual cortex (VC) is a major source of sensory information to the hippocampus, information processing in the cortex may affect hippocampal network oscillations, facilitating the induction of synaptic modifications. We investigated to what degree the field activity in the primary VC, elicited by sensory or electrical stimulation, correlates with hippocampal oscillatory and synaptic responsiveness, in freely behaving adult rats. We found that the spectral power of theta rhythm (4–10 Hz) in the dentate gyrus (DG), increases in parallel with high-frequency oscillations in layer 2/3 of the VC and that this correlation depends on the degree of exploratory activity. When we mimic robust thalamocortical activity by theta-burst application to dorsal lateral geniculate nucleus, a hippocampal theta increase occurs, followed by a persistent potentiation of the DG granule field population spike. Furthermore, the potentiation of DG neuronal excitability tightly correlates with the concurrently occurring VC plasticity. The concurrent enhancement of VC and DG activity is also combined with a highly negative synchronization between hippocampal and cortical low-frequency oscillations. Exploration of familiar environment decreases the degree of this synchrony. Our data propose that novel visual information can induce high-power fluctuations in intrinsic excitability for both VC and hippocampus, potent enough to induce experience-dependent modulation of cortico-hippocampal connections. This interaction may comprise one of the endogenous triggers for long-term synaptic plasticity in the hippocampus

Strain-Dependent Variations in Spatial Learning and in Hippocampal Synaptic Plasticity in the Dentate Gyrus Of Freely Behaving Rats

Hippocampal synaptic plasticity is believed to comprise the cellular basis for spatial learning. Strain-dependent differences in synaptic plasticity in the CA1 region have been reported. However, it is not known whether these differences extend to other synapses within the trisynaptic circuit, although there is evidence for morphological variations within that path. We investigated whether Wistar and Hooded Lister (HL) rat strains express differences in synaptic plasticity in the dentate gyrus in vivo. We also explored whether they exhibit differences in the ability to engage in spatial learning in an eight-arm radial maze. Basal synaptic transmission was stable over a 24-h period in both rat strains, and the input–output relationship of both strains was not significantly different. Paired-pulse analysis revealed significantly less paired-pulse facilitation in the HL strain when pulses were given 40–100 ms apart. Low frequency stimulation at 1 Hz evoked long-term depression (>24 h) in Wistar and short-term depression (<2 h) in HL rats; 200 Hz stimulation induced long-term potentiation (>24 h) in Wistar, and a transient, significantly smaller potentiation (<1 h) in HL rats, suggesting that HL rats have higher thresholds for expression of persistent synaptic plasticity. Training for 10 days in an eight-arm radial maze revealed that HL rats master the working memory task faster than Wistar rats, although both strains show an equivalent performance by the end of the trial period. HL rats also perform more efficiently in a double working and reference memory task. On the other hand, Wistar rats show better reference memory performance on the final (8–10) days of training. Wistar rats were less active and more anxious than HL rats. These data suggest that strain-dependent variations in hippocampal synaptic plasticity occur in different hippocampal synapses. A clear correlation with differences in spatial learning is not evident however

Relationship of Hippocampal Theta and Gamma Oscillations to Potentiation of Synaptic Transmission

In the hippocampus in vivo, both synaptic plasticity and network activity are closely interdependent. We have found that immediately after an attempt to induce long-term potentiation (LTP), changes in theta (5–10 Hz) and gamma (30–100 Hz) activity correlate tightly with the occurrence of LTP, suggesting that tetanisation-driven activation of sensory inputs synchronises the activity of granule cells and interneurons, and thus, facilitates the encoding of acquired stimuli. This results in increase of theta and gamma power, and elevates the probability that afferent stimuli both coincide with the peak of theta cycle and reach their post-synaptic target within the gamma time-window (of 10–30 ms). Both these mechanisms can effectively shift the direction, of tetanisation-induced changes in synaptic weight, towards potentiation and induction of LTP. Here, we discuss our findings in the context of possible mechanisms that link theta and gamma oscillations with LTP induction, as well as their role in information processing and formation of memories

Involvement of the Metabotropic Glutamate Receptor mGluR5 in NMDA Receptor-Dependent, Learning-Facilitated Long-Term Depression in CA1 Synapses

Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with persistent synaptic plasticity to the coupling of weak afferent stimulation, which is subthreshold for the induction of plasticity, with a spatial learning experience. The metabotropic glutamate receptor subtype 5 (mGluR5) is critically involved in enabling the persistency of multiple forms of hippocampal synaptic plasticity. We compared the effects of pharmacological allosteric antagonism of mGluR5 in learning-facilitated plasticity with plasticity that had been induced solely by patterned afferent stimulation of the Schaffer collateral pathway to the CA1 stratum radiatum of adult freely behaving rats. Intracerebroventricular injection of the selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) had no effect on basal synaptic transmission but significantly prevented both long-term depression (LTD) elicited by electrical stimulation and LTD facilitated by novel object-place configuration learning. NMDA receptor antagonism also prevented learning-facilitated LTD. Habituation to the objects was prevented by MPEP application. Whereas reexposure to the object-place configuration (after 7 days) failed to facilitate LTD in control animals, those who had been treated previously with MPEP expressed LTD, suggesting that inhibition of learning contributed to the initial prevention of LTD. These data support a pivotal role for mGluR5 in both hippocampal LTD and the acquisition of object-place configurations

Distinct Time-Course of Alterations of Groups I and II Metabotropic Glutamate Receptor and GABAergic Receptor Expression Along the Dorsoventral Hippocampal Axis in an Animal Model of Psychosis

Psychosis is a clinical state that encompasses a range of abnormal conditions, including distortions in sensory information processing and the resultant delusional thinking, emotional discordance and cognitive impairments. Upon developing this condition, the rate at which cognitive and behavioral deteriorations progress steadily increases suggesting an active contribution of the first psychotic event to the progression of structural and functional abnormalities and disease establishment in diagnosed patients. Changes in GABAergic and glutamatergic function, or expression, in the hippocampus have been proposed as a key factor in the pathophysiology of psychosis. However, little is known as to the time-point of onset of putative changes, to what extent they are progressive, and their relation to disease stabilization. Here, we characterized the expression and distribution patterns of groups I and II metabotropic glutamate (mGlu) receptors and GABA receptors 1 week and 3 months after systemic treatment with an N-methyl-D-aspartate receptor (NMDAR) antagonist (MK801) that is used to model a psychosis-like state in adult rats. We found an early alteration in the expression of mGlu1, mGlu2/3, and GABAB receptors across the hippocampal dorsoventral and transverse axes. This expanded to include an up-regulation of mGlu5 levels across the entire CA1 region and a reduction in GABAB expression, as well as GAD67-positive interneurons particularly in the dorsal hippocampus that appeared 3 months after treatment. Our findings indicate that a reduction of excitability may occur in the hippocampus soon after first-episode psychosis. This changes, over time, into increased excitability. These hippocampus-specific alterations are likely to contribute to the pathophysiology and stabilization of psychosis

Frequency Facilitation at Mossy Fiber–CA3 Synapses of Freely Behaving Rats Contributes to the Induction of Persistent LTD via an Adenosine-A1 Receptor-Regulated Mechanism

Frequency facilitation (FF), comprising a rapid and multiple-fold increase in the magnitude of evoked field potentials, is elicited by low-frequency stimulation (LFS) at mossy fiber–CA3 synapses. Here, we show that in freely behaving rats, FF reliably occurs in response to 1 and 2Hz but not in response to 0.25-, 0.3-, or 0.5-Hz LFS. Strikingly, prolonged (∼600 s) FF was tightly correlated to the induction of long-term depression (LTD) in freely moving animals. Although LFS at 2 Hz elicited unstable FF and unstable LTD, application of LFS at 1 Hz elicited pronounced FF, as well as robust LTD that persisted for over 24 h. This correlation of prolonged FF with LTD was absent at stimulation frequencies that did not induce FF. The adenosine-A1 receptor appears to participate in these effects: Application of adenosine-A1, but not adenosine-A3, receptor antagonists enhanced mossy fiber synaptic transmission and occluded FF. Furthermore, adenosine-A1 receptor antagonism resulted in more stable FF at 1 or 2 Hz and elicited more potent LTD. These data support the fact that FF contributes to the enablement of long-term information storage at mossy fiber–CA3 synapses and that the adenosine-A1 receptor may regulate the thresholds for this process