Enhanced recognition memory following glycine transporter 1 deletion in forebrain neurons.

Abstract

Selective deletion of glycine transporter 1 (GlyT1) in forebrain neurons enhances N-methyl-D-aspartate receptor (NMDAR)-dependent neurotransmission and facilitates associative learning. These effects are attributable to increases in extracellular glycine availability in forebrain neurons due to reduced glycine re-uptake. Using a forebrain- and neuron-specific GlyT1-knockout mouse line (CamKIIalphaCre; GlyT1tm1.2fl/fI), the authors investigated whether this molecular intervention can affect recognition memory. In a spontaneous object recognition memory test, enhanced preference for a novel object was demonstrated in mutant mice relative to littermate control subjects at a retention interval of 2 hr, but not at 2 min. Furthermore, mutants were responsive to a switch in the relative spatial positions of objects, whereas control subjects were not. These potential procognitive effects were demonstrated against a lack of difference in contextual novelty detection: Mutant and control subjects showed equivalent preference for a novel over a familiar context. Results therefore extend the possible range of potential promnesic effects of specific forebrain neuronal GlyT1 deletion from associative learning to recognition memory and further support the possibility that mnemonic functions can be enhanced by reducing GlyT1 function.

Deletion of glycine transporter 1 (GlyT1) in forebrain neurons facilitates reversal learning: Enhanced cognitive adaptability?

“…The latter may be by design, as in the discrimination reversal experiment here, or perhaps accidental as the results by Duffy et al (2008) seem to suggest. This is noteworthy because our previous demonstration of enhanced object recognition memory in the CamKIIαCre;GlyT1tm1.2fl/fl mice was also against the background of a complete lack of novelty preference in the control mice (Singer et al, 2007). This was achieved at a delay retention interval of two hours, which should still yield appreciable novelty preference in wild type C57BL/6 mice according to some studies (e.g., Hale & Good, 2005).…”

Spontaneous object recognition and its relevance to schizophrenia: a review of findings from pharmacological, genetic, lesion and developmental rodent models

“…GMS (partial) agonists are thus being investigated as potential adjunctive therapies in schizophrenia. While mice that lacked the synthetic enzyme for D-serine were not impaired in SOR with a 1-min delay (Devito et al 2010), mice that lacked GlyT1 in forebrain neurons showed better SOR performance than wild-type controls with a 2-h delay (Singer et al 2007). Importantly, the GlyT1 knockout mice did not show enhanced performance with a 2-min delay, increasing confidence that the improvement seen after 2 h reflects a specific effect on memory.…”

Selective Blockade of Dopamine D3 Receptors Enhances while D2 Receptor Antagonism Impairs Social Novelty Discrimination and Novel Object Recognition in Rats: A Key Role for the Prefrontal Cortex

“…Additionally, bilateral microinjection of the dopamine D 1 receptor antagonist, SCH23390, into the PFC of mice altered recognition memory and increased ERK1/2 phosphorylation therein (Nagai et al, 2007). Facilitation of NMDA receptor-dependent neurotransmission by the selective deletion of forebrain glycine transporter 1 (GlyT1) also enhances object recognition (Singer et al, 2007) and social cognition (Shimazaki et al, 2010). Collectively, this suggest that although the PFC may not be critical for task performance, it exerts a powerful modulatory effect on NOR.…”