Biomedical subjects

Eugenio Aztiria

Publications and source records attributed to Eugenio Aztiria.

5 recordsLinked to original sources

PubMed2006

Muscarinic acetylcholine receptor knockout mice show distinct synaptic plasticity impairments in the visual cortex.

In the present report, we focused our attention on the role played by the muscarinic acetylcholine receptors (mAChRs) in different forms of long-term synaptic plasticity. Specifically, we investigated long-term potentiation (LTP) and long-term depression (LTD) expression elicited by theta-burst stimulation (TBS) and low-frequency stimulation (LFS), respectively, in visual cortical slices obtained from different mAChR knockout (KO) mice. A normal LTP was evoked in M(1)/M(3) double KO mice, while LTP was impaired in the M(2)/M(4) double KO animals. On the other hand, LFS induced LTD in M(2)/M(4) double KO mice, but failed to do so in M(1)/M(3) KO mice. Interestingly, LFS produced LTP instead of LTD in M(1)/M(3) KO mice. Analysis of mAChR single KO mice revealed that LTP was affected only by the simultaneous absence of both M(2) and M(4) receptors. A LFS-dependent shift from LTD to LTP was also observed in slices from M(1) KO mice, while LTD was simply abolished in slices from M(3) KO mice. Using pharmacological tools, we showed that LTP in control mice was blocked by pertussis toxin, an inhibitor of G(i/o) proteins, but not by raising intracellular cAMP levels. In addition, the inhibition of phospholipase C by U73122 induced the same shift from LTD to LTP after LFS observed in M(1) single KO and M(1)/M(3) double KO mice. Our results indicate that different mAChR subtypes regulate different forms of long-term synaptic plasticity in the mouse visual cortex, activating specific G proteins and downstream intracellular mechanisms.

Animals↗

PubMed2006

Developmental modulation of synaptic transmission by acetylcholine in the primary visual cortex.

Despite the evidence that cortical synaptic organization and cognitive functions are influenced by the activity of the cholinergic system during postnatal development, so far no information is available on the effects produced by acetylcholine (ACh) on synaptic transmission. In the present article, we show that the ability of visual cortex slices to respond to ACh depends on postnatal age. In adulthood, ACh exerts mainly a facilitatory action on synaptic transmission, depressing field potential (FP) amplitude only if applied at high concentrations (millimolar range). During early postnatal development, at postnatal day 13 (P13), facilitation by ACh was lacking, with depression of FP observed with concentration of ACh in the micromolar range. The magnitude of ACh facilitatory effects increases with age. The time course of ACh-dependent facilitation overlaps the developmental maturation of acetylcholinesterase (AChE), suggesting a close relationship between ACh action and AChE activity. Thus, age-dependent modification of the cholinergic modulatory action may affect cortical maturation by regulating the magnitude of synaptic transmission.

Acetylcholine↗

PubMed2005

Reduction of GFAP induced by long dark rearing is not restricted to visual cortex.

A key component of the astrocyte cytoskeleton is the glial fibrillary acidic protein (GFAP), which plays an essential role in neuron/astrocyte interactions. Environmental conditioning, such as visual experience manipulation, can affect neuronal and/or glial plasticity in specific brain areas. Previous work from our laboratory showed that short light deprivation throughout the period of GFAP maturation does not influence the expression profile of GFAP in mouse visual cortex; however, it was strong enough to affect neuronal phenotype. It was suggested that visual experience controls the maturation of the neuronal circuitry in this brain area. Therefore, to see whether the modifications of neuronal activity induced by light deprivation affect the maintenance of normal astrocytic phenotype, the dark rearing protocol was extended until the adult life. GFAP-immunoreactive cells were dramatically affected, showing an 80% decrease in number. In addition, GFAP protein level exhibited a 50% reduction, while its mRNA remained unaffected. Besides the visual cortex, two other areas of the brain not directly involved in vision, the hippocampus and the motor cortex, were chosen as internal controls. Unexpectedly, also in these areas, astrocytes were affected by light deprivation. The present results show that lack of visual experience for long periods of time deeply affects glial phenotype not only in visual areas but also in brain regions not directly involved in sensory processing.

Animals↗

PubMed2005

Acetylcholine modulates cortical synaptic transmission via different muscarinic receptors, as studied with receptor knockout mice.

The central cholinergic system plays a crucial role in synaptic plasticity and spatial attention; however, the roles of the individual cholinergic receptors involved in these activities are not well understood at present. In the present study, we show that acetylcholine (ACh) can facilitate or depress synaptic transmission in occipital slices of mouse visual cortex. The precise nature of the ACh effects depends on the ACh concentration, and is input specific, as shown by stimulating different synaptic pathways. Pharmacological blockade of muscarinic receptor (mAChR) subtypes and the use of M1-M5 mAChR-deficient mice showed that specific mAChR subtypes, together with the activity of the cholinesterases (ChEs), mediate facilitation or depression of synaptic transmission. The present data suggest that local ACh, acting through mAChRs, regulates the cortical dynamics making cortical circuits respond to specific stimuli.

Acetylcholine↗

PubMed2004

Alpha7 but not alpha4 AChR subunit expression is regulated by light in developing primary visual cortex.

In the present paper we analyzed the expression pattern of the alpha4 and alpha7 nicotinic acetylcholine receptor (nAChR) subunits in the rat visual cortex through postnatal development, to clarify whether their expression is developmentally regulated and whether eventual developmental changes are regulated by visual experience. We found that both alpha4 and alpha7 mRNA levels accumulate from postnatal day 12 (P12) before eye opening, to around P35. The immunohistochemical results indicated that both subunits are expressed throughout all cortical laminae, except layer I. Alpha4 subunit immunohistochemistry revealed significant increments in the number of positive cells in layers V and VI after eye opening. In the case of the alpha7 subunit, the number of immunoreactive cells increased in all cortical layers soon after eye opening, except in layer VI, matching the results found at the transcriptional level. In animals reared in darkness from P9 to P22, the relative amount of the alpha4 mRNA and the number of immunoreactive cells exhibited no changes. 3H-epibatidine binding experiments showed that the number of heteromeric nAChR subunits in dark-reared rats did not change with respect to age-matched controls, thus confirming the immunohistochemical results. The mRNA of the alpha7 subunit remained stable in dark-reared rats, whereas the number and distribution of immunoreactive cells changed. Moreover, the number of 125I alphabungarotoxin-binding nAChRs was significantly increased in dark-reared animals. These results indicate that visual cortex stimulation by visual input is an essential step for alpha7 nAChR normal expression, suggesting a possible role for these receptors in an experience-dependent fashion on the maturation of this cortical area.

Age Factors↗