Biomedical subjects

Aaron R Best

Publications and source records attributed to Aaron R Best.

5 recordsLinked to original sources

PubMed2006

Sustained elevation of dendritic calcium evokes widespread endocannabinoid release and suppression of synapses onto cerebellar Purkinje cells.

Endocannabinoids can act as retrograde messengers that allow postsynaptic cells to regulate the strength of their synaptic inputs. In the cerebellum, Purkinje cells (PCs) release endocannabinoids through two mechanisms. Synaptic activation evokes local endocannabinoid release that relies on a pathway that involves the metabotropic glutamate receptor mGluR1 and phospholipase-C (PLC). In contrast, depolarization evokes endocannabinoid release from the entire dendritic arbor. This leads to depolarization-induced suppression of inhibitory (DSI) and excitatory (DSE) synapses by a mechanism that does not involve mGluR1 or PLC. This latter mechanism of endocannabinoid release has only been observed under artificial conditions that transiently elevate postsynaptic calcium to >5 microm. Here, we tested the possibility that this mechanism could lead to retrograde inhibition in response to more realistic calcium signals. At both climbing fiber and inhibitory synapses onto PCs, we found that prolonging the elevation of calcium significantly lowered the peak calcium required to evoke PLC-independent endocannabinoid release. This suggests that the mechanism of endocannabinoid release involved in DSI and DSE is likely to evoke endocannabinoid release in response to physiologically relevant levels of calcium. When dendritic calcium was elevated to 0.4-1 microm for 15 s or more, endocannabinoid release from PCs selectively suppressed inhibitory synapses. This suggests that inhibitory synapses are more sensitive to prolonged calcium increases. Thus, in contrast to localized retrograde inhibition evoked by synaptic activation, modest but sustained calcium elevation could globally suppress inhibitory synapses onto PCs.

Animals↗

PubMed2005

Ontogeny of cortical synaptic depression underlying olfactory sensory gating in the rat.

Sensory gating is the ability to filter irrelevant or redundant sensory input and is a critical function of all sensory systems that allows efficient processing of important stimuli. The present results demonstrate that a form of activity-dependent synaptic depression recently found to be involved in both cortical and behavioral olfactory sensory gating, is functional by at least the first postnatal week in the rat piriform cortex, and shares a common metabotropic glutamate receptor mechanism.

Animals↗

PubMed2005

Cortical metabotropic glutamate receptors contribute to habituation of a simple odor-evoked behavior.

Defining the circuits that are involved in production and cessation of specific behaviors is an ultimate goal of neuroscience. Short-term behavioral habituation is the response decrement observed in many behaviors that occurs during repeated presentation of non-reinforced stimuli. Within a number of invertebrate models of short-term behavioral habituation, depression of a defined synapse has been implicated as the mechanism. However, the synaptic mechanisms of short-term behavioral habituation have not been identified within mammals. We have shown previously that a presynaptic metabotropic glutamate receptor (mGluR)-dependent depression of synapses formed by olfactory bulb afferents to the piriform (olfactory) cortex significantly contributes to adaptation of cortical odor responses. Here we show that blockade of mGluRs within the olfactory cortex of awake, behaving rats diminishes habituation of a simple odor-induced behavior, strongly implicating a central mechanism for sensory gating in olfaction.

Animals↗

PubMed2005

High-frequency oscillations are not necessary for simple olfactory discriminations in young rats.

Individual olfactory bulb mitral/tufted cells respond preferentially to groups of molecularly similar odorants. Bulbar interneurons such as periglomerular and granule cells are thought to influence mitral/tufted odorant receptive fields through mechanisms such as lateral inhibition. The mitralgranule cell circuit is also important in the generation of the odor-evoked fast oscillations seen in the olfactory bulb local field potentials and hypothesized to be an important indicator of odor quality coding. Infant rats, however, lack a majority of these inhibitory interneurons until the second week of life. It is unclear if these developmental differences affect olfactory bulb odor coding or behavioral odor discrimination. The following experiments are aimed at better understanding odor coding and behavioral odor discrimination in the developing olfactory system. Single-unit recordings from mitral/tufted cells and local field-potential recordings from both the olfactory bulb and anterior piriform cortex were performed in freely breathing urethane-anesthetized rats (postnatal day 7 to adult). Age-dependent behavioral odor discrimination to a homologous series of ethyl esters was also examined using a cross-habituation paradigm. Odorants were equated in all experiments for concentration (150 ppm) using a flow dilution olfactometer. In concordance with the reduced interneuron population, local field potentials in neonates lacked detectable odor-evoked gamma-frequency oscillations that were observed in mature animals. However, mitral/tufted cell odorant receptive fields and behavioral odor discrimination did not significantly change, despite known substantial changes in local circuitry and neuronal populations, over the age range examined. The results suggest that high-frequency local field-potential oscillations do not reflect processes critical for simple odor discrimination.

Action Potentials↗

PubMed2004

Coordinate synaptic mechanisms contributing to olfactory cortical adaptation.

Anterior piriform cortex (aPCX) neurons rapidly filter repetitive odor stimuli despite relatively maintained input from mitral cells. This cortical adaptation is correlated with short-term depression of afferent synapses, in vivo. The purpose of this study was to elucidate mechanisms underlying this nonassociative neural plasticity using in vivo and in vitro preparations and to determine its role in cortical odor adaptation. Lateral olfactory tract (LOT)-evoked responses were recorded in rat aPCX coronal slices. Extracellular and intracellular potentials were recorded before and after simulated odor stimulation of the LOT. Results were compared with in vivo intracellular recordings from aPCX layer II/III neurons and field recordings in urethane-anesthetized rats stimulated with odorants. The onset, time course, and extent of LOT synaptic depression during both in vitro electrical and in vivo odorant stimulation methods were similar. Similar to the odor specificity of cortical odor adaptation in vivo, there was no evidence of heterosynaptic depression between independent inputs in vitro. In vitro evidence suggests at least two mechanisms contribute to this activity-dependent synaptic depression: a rapidly recovering presynaptic depression during the initial 10-20 sec of the post-train recovery period and a longer lasting (approximately 120 sec) depression that can be blocked by the metabotropic glutamate receptor (mGluR) II/III antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG) and by the beta-adrenergic receptor agonist isoproterenol. Importantly, in line with the in vitro findings, both adaptation of odor responses in the beta (15-35 Hz) spectral range and the associated synaptic depression can also be blocked by intracortical infusion of CPPG in vivo.

Adaptation, Physiological↗