Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The axons of the neurons in the medial and lateral components of the entorhinal cortex (MEC and LEC) form the medial and lateral perforant paths (MPP and LPP) which represent the major source of cortical input to the hippocampus. Anatomical, physiological, and pharmacological studies have shown that MPP and LPP are distinct. Unfortunately, assessment of the functional significance of damage to either of these pathways has not used tasks known to be sensitive to hippocampal function in the rodent. In this study, we performed dissociated lesions of MPP and LPP using a combined physiological and anatomical method. Rats with lesions of either the MPP or the LPP were tested on place learning in the water task and on a discriminative fear conditioning to context task. The results indicated that the MPP, but not LPP, lesions resulted in impaired place learning. The context discrimination data revealed an amygdala-like, reduced fear effect of MPP lesions and an enhanced discriminative fear conditioning to context effect of LPP lesions. Consistent with a two-stage model of spatial learning proposed by Buzsaki (Buzsaki G. Two-stage model of memory trace formation: a role for 'noisy' brain states. Neuroscience 1989;31(3):551-570), the impairment in the water task can be interpreted as reflecting the higher efficiency of the MPP synapses in activating hippocampal neurons. The context discrimination results can be explained by either a dissociation of sensory information that reaches the MEC and LEC, or alternatively, by a dissociation between the limbic nature of the MEC and the sensory nature of the LEC.
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PMID:Lesions of the medial or lateral perforant path have different effects on hippocampal contributions to place learning and on fear conditioning to context. 1034 1

The entorhinal cortex (EC) is divided into medial (MEC) and lateral (LEC) anatomical areas, and layer II neurons of these two regions project to granule cells of the dentate gyrus through the medial and lateral perforant pathways (MPP and LPP), respectively. Stellate cells (SCs) represent the main neurons constituting the MPP inputs, while fan cells (FCs) represent the main LPP inputs. Here, we first characterized the excitability properties of SCs and FCs in adult wild-type (WT) mouse brain. Our data indicate that, during sustained depolarization, action potentials (APs) generated by SCs exhibit increased fast afterhyperpolarization and overshoot, making them able to fire at higher frequencies and to exhibit higher spike frequency adaptation (SFA) than FCs. Since the EC is one of the earliest brain regions affected during Alzheimer's disease (AD) progression, we compared SCs and FCs firing in 4-month-old WT and transgenic Tg2576 mice, a well-established AD mouse model. Tg2576-SCs displayed a slight increase in firing frequency during mild depolarization but otherwise normal excitability properties during higher stimulations. On the contrary, Tg2576-FCs exhibited a decreased firing frequency during mild and higher depolarizations, as well as an increased SFA. Our data identify the FCs as a neuronal population particularly sensitive to early pathological effects of chronic accumulation of APP-derived peptides, as it occurs in Tg2576 mice. As FCs represent the major input of sensory information to the hippocampus during memory acquisition, early alterations in their excitability profile could significantly contribute to the onset of cognitive decline in AD.
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PMID:Firing properties of entorhinal cortex neurons and early alterations in an Alzheimer's disease transgenic model. 2413 29