Immature doublecortin-positive hippocampal neurons are important for learning but not for remembering.

It is now widely accepted that hippocampal neurogenesis underpins critical cognitive functions, such as learning and memory. To assess the behavioral importance of adult-born neurons, we developed a novel knock-in mouse model that allowed us to specifically and reversibly ablate hippocampal neurons at an immature stage. In these mice, the diphtheria toxin receptor (DTR) is expressed under control of the doublecortin (DCX) promoter, which allows for specific ablation of immature DCX-expressing neurons after administration of diphtheria toxin while leaving the neural precursor pool intact.

Alzheimer brain-derived amyloid β-protein impairs synaptic remodeling and memory consolidation.

Aggregation of the amyloid β-protein (Aβ) is believed to play a central role in initiating the molecular cascade that culminates in Alzheimer-type dementia (AD), a disease which in its early stage is characterized by synaptic loss and impairment of episodic memory. Here we show that intracerebroventricular injection of Aβ-containing water-soluble extracts of AD brain inhibits consolidation of the memory of avoidance learning in the rat and that this effect is highly dependent on the interval between learning and administration. When injected at 1 hour post training extracts from 2 different AD brains significantly impaired recall tested at 48 hours.

Inducible cAMP early repressor (ICER) and brain functions.

The inducible cAMP early repressor (ICER) is an endogenous repressor of cAMP-responsive element (CRE)-mediated gene transcription and belongs to the CRE-binding protein (CREB)/CRE modulator (CREM)/activating transcription factor 1 (ATF-1) gene family. ICER plays an important role in regulating the neuroendocrine system and the circadian rhythm. Other aspects of ICER function have recently attracted heightened attention.

Inducible cAMP early repressor acts as a negative regulator for kindling epileptogenesis and long-term fear memory.

Long-lasting neuronal plasticity as well as long-term memory (LTM) requires de novo synthesis of proteins through dynamic regulation of gene expression. cAMP-responsive element (CRE)-mediated gene transcription occurs in an activity-dependent manner and plays a pivotal role in neuronal plasticity and LTM in a variety of species. To study the physiological role of inducible cAMP early repressor (ICER), a CRE-mediated gene transcription repressor, in neuronal plasticity and LTM, we generated two types of ICER mutant mice: ICER-overexpressing (OE) mice and ICER-specific knock-out (KO) mice.

Repeated withdrawal from ethanol spares contextual fear conditioning and spatial learning but impairs negative patterning and induces over-responding: evidence for effect on frontal cortical but not hippocampal function?

Repeated exposure of rats to withdrawal from chronic ethanol reduces hippocampal long-term potentiation and gives rise to epileptiform-like activity in hippocampus. We investigated whether such withdrawal experience also affects learning in tasks thought to be sensitive to hippocampal damage. Rats fed an ethanol-containing diet for 24 days with two intermediate 3-day withdrawal episodes, resulting in intakes of 13-14 g/kg ethanol per day, showed impaired negative patterning discrimination compared with controls and animals that had continuous 24-day ethanol treatment, but did not differ from these animals in the degree of contextual freezing 24 h after training or in spatial learning in the Barnes maze.