Hippocampus
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It has been well established that the hippocampal formation plays a critical role in the formation of memories. However, functional specialization within the hippocampus remains controversial. Using functional magnetic resonance imaging (fMRI) during a face-name associative encoding task, followed by a postscan recognition test for face memory and face-name pair memory, we investigated the roles of anterior and posterior hippocampal regions in successful encoding of associations and items. ⋯ In contrast, the posterior hippocampal formation showed activation above baseline during attempted encoding of face-name pairs, but no evidence of differential activation based on subsequent memory. Furthermore, exploratory whole-brain analyses revealed that a parahippocampal region, most likely corresponding to perirhinal cortex, showed subsequent memory effects for faces. These data provide evidence for functional specialization within the hippocampal formation based on the associative nature of the stimuli and subsequent memory.
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Theta-frequency (4-12 Hz) electroencephalographic activity is thought to play a role in mechanisms mediating sensory and mnemonic processing in the entorhinal cortex and hippocampus, but the effects of acetylcholine on excitatory synaptic inputs to the entorhinal cortex are not well understood. Field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of the piriform (olfactory) cortex were recorded in the medial entorhinal cortex during behaviors associated with theta activity (active mobility) and were compared with those recorded during nontheta behaviors (awake immobility and slow wave sleep). Synaptic responses were smaller during behavioral activity than during awake immobility and sleep, and responses recorded during movement were largest during the negative phase of the theta rhythm. ⋯ The GABA(A) receptor-blocker bicuculline (50 microM) did not prevent the cholinergic suppression of EPSPs, suggesting that the suppression is not dependent on inhibitory mechanisms. Paired-pulse facilitation of field and intracellular EPSPs were enhanced by carbachol, indicating that the suppression is likely due to inhibition of presynaptic glutamate release. These results indicate that, in addition to well known effects on postsynaptic conductances that increase cellular excitability, cholinergic activation in the entorhinal cortex results in a strong reduction in strength of excitatory synaptic inputs from the piriform cortex.
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Acetylcholine (ACh) acts as a neurotransmitter in both the hippocampus and neocortex to facilitate learning, memory, and cognitive function. Here we show that transient muscarinic ACh receptor (mAChR) activation inhibits action potential generation in CA1, but not in CA3, pyramidal neurons via activation of an SK-type calcium-activated potassium conductance. Hyperpolarizing responses generated by focal ACh application near the somata of CA1 pyramidal neurons were blocked by atropine or the M1-like mAChR antagonist pirenzepine, but not by the M2-like mAChR antagonist methoctramine. ⋯ Cholinergic inhibition did not require GABAergic synaptic transmission, but was blocked by apamin, an SK channel antagonist. In contrast to inhibitory effects in CA1 neurons, ACh was primarily depolarizing, and enhanced action potential firing in CA3 pyramidal neurons. These results, when combined with recent data in neocortical neurons, suggest a functional homology in phasic cholinergic signaling in the hippocampus and neocortex whereby ACh preferentially inhibits those neurons in the lower cortical layers (CA1 and layer 5 neurons) that provide the majority of extracortical efferent projections.
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Some studies suggest that the histaminergic system plays an important role in learning and memory. However, the results seem to be controversial in many behavioral tasks. In the present study, we used HDC knockout (HDC-KO) mice to investigate the effects of long-term histamine deficiency on learning and memory in contextual fear conditioning. ⋯ The results indicated that histamine deficiency may improve consolidation of contextual fear conditioning. This improvement may be due to the increased hippocampal CA1 LTP, and presynaptic glutamate release. The relationship between behavior and synaptic plasticity provides support for the involvement of activity-dependent LTP in learning and memory.
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Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline due to neuronal loss and neural network dysfunction. It has been postulated that progressive neuronal loss in AD is consequence of the neurotoxic properties of the amyloid-beta peptide (Abeta). In the present study, we investigated the effect of T-817MA (1-{3-[2-(1-benzothiophen-5-yl)ethoxy] propyl}-3-azetidinol maleate), a newly synthesized neurotrophic compound, on place learning deficits in rats with hippocampal damages. ⋯ Furthermore, T-817MA prevented granule cell loss due to Abeta-infusion, which was correlated to task performance of the rats. However, other cognitive enhancer, an acetylcholinesterase inhibitor, had no such effects. The results demonstrated that T-817MA ameliorated learning deficits induced by Abeta infusion, which might be attributed to neuroprotection in the hippocampus.