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In JoVE (1)
Other Publications (8)
- Neurotoxicity Research
- Journal of Neuroscience Methods
- Neuron
- Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
- Optics Express
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- Frontiers in Neural Circuits
- Journal of Neuroscience Methods
Articles by Hirac Gurden in JoVE
JoVE Neuroscience
Imaging Odor-Evoked Activities in the Mouse Olfactory Bulb using Optical Reflectance and Autofluorescence Signals
This article presents the protocols of intrinsic optical signals and flavoproteins autofluorescence signals imaging to map odor-evoked activities at the surface of the olfactory bulb in mice.
Other articles by Hirac Gurden on PubMed
Plasticity at Hippocampal to Prefrontal Cortex Synapses is Impaired by Loss of Dopamine and Stress: Importance for Psychiatric Diseases
The direct hippocampal to prefrontal cortex pathway and its changes in synaptic plasticity is a useful framework for investigating the functional operations of hippocampal-prefrontal cortex communication in cognitive functions. Synapses on this pathway are modifiable and synaptic strength can be turned up or down depending on specific patterns of activity in the pathway. The objective of this review will be to summarize the different studies carried out on this topic including very recent data and to underline the importance of animal models for the development of new and effective medications in psychiatric diseases. We have shown that long-term potentiation (LTP) of hippocampal-prefrontal synapses is driven by the level of mesocortical dopaminergic (DA) activity and more recently that stress is also an environmental determinant of LTP at these cortical synapses. Stimulation of the ventral tegmental area at a frequency known to evoke DA overflow in the prefrontal cortex produces a long-lasting enhancement of the magnitude of hippocampal-prefrontal cortex LTP whereas a depletion of cortical DA levels generates a dramatic decrease in this LTP. Moreover, hippocampal stimulation induces a transient but significant increase in DA release in the prefrontal cortex and an optimal level of D1 receptor activation is essential for LTP expression. We recently investigated the impact of stress on hippocampal-prefrontal LTP and demonstrated that exposure to an acute stress causes a remarkable and long-lasting inhibition of LTP. Furthermore, we demonstrated that tianeptine, an antidepressant which has a unique mode of action, and clozapine an atypical antipsychotic when administered at doses normally used in human testing are able to reverse the impairment in LTP. Stressful life events have a substantial causal association with psychiatric disorders like schizophrenia and depression and recent imaging studies have shown an important role of the limbic-cortical circuit in the pathophysiology of these illnesses. Therefore, we proposed that agents capable of reversing the impairment of plasticity at hippocampal to prefrontal cortex synapses have the potential of becoming new therapeutic classes of antidepressant or antipsychotic drugs.
Combining the Radiosensitive Beta MicroProbe to Nuclear Magnetic Resonance: Theoretical Approach for in Vivo Studies in Small Animals
In vivo small animal imaging with multiple modalities has become an important tool in modern biomedical research. Indeed, combining exploratory techniques allows simultaneous recording of complementary data, which is required to elucidate complex physiopathological mechanisms. In this field, because of strict technical constraints in vivo, an exciting challenge remains in the combination of Nuclear Magnetic Resonance (NMR) and Positron Emission Tomography (PET). Coupling NMR with a radiosensitive Beta MicroProbe offers therefore a very interesting technical alternative. Here, we assessed the feasibility of this new combination by theoretically evaluating the ability of the Beta MicroProbe to monitor radioactivity in a magnet. To that aim, we modelled with Geant4 the effect of an intense magnetic field on the probe field of view and showed that the field should not have an impact on the global efficiency of the probe.
Sensory-evoked Intrinsic Optical Signals in the Olfactory Bulb Are Coupled to Glutamate Release and Uptake
Functional imaging signals arise from metabolic and hemodynamic activity, but how these processes are related to the synaptic and electrical activity of neurons is not well understood. To provide insight into this issue, we used in vivo imaging and simultaneous local pharmacology to study how sensory-evoked neural activity leads to intrinsic optical signals (IOS) in the well-defined circuitry of the olfactory glomerulus. Odor-evoked IOS were tightly coupled to release of glutamate and were strongly modulated by activation of presynaptic dopamine and GABA-B receptors. Surprisingly, IOS were independent of postsynaptic transmission through ionotropic or metabotropic glutamate receptors, but instead were inhibited when uptake by astrocytic glutamate transporters was blocked. These data suggest that presynaptic glutamate release and uptake by astrocytes form a critical pathway through which neural activity is linked to metabolic processing and hence to functional imaging signals.
The Potential of a Radiosensitive Intracerebral Probe to Monitor 18F-MPPF Binding in Mouse Hippocampus in Vivo
As mouse imaging has become more challenging in preclinical research, efforts have been made to develop dedicated PET systems. Although these systems are currently used for the study of physiopathologic murine models, they present some drawbacks for brain studies, including a low temporal resolution that limits the pharmacokinetic study of radiotracers. The aim of this study was to demonstrate the ability of a radiosensitive intracerebral probe to measure the binding of a radiotracer in the mouse brain in vivo.
Autofluorescence Imaging of NADH and Flavoproteins in the Rat Brain: Insights from Monte Carlo Simulations
There has been recently a renewed interest in using Autofluorescence imaging (AF) of NADH and flavoproteins (Fp) to map brain activity in cortical areas. The recording of these cellular signals provides complementary information to intrinsic optical imaging based on hemodynamic changes. However, which of NADH or Fp is the best candidate for AF functional imaging is not established, and the temporal profile of AF signals is not fully understood. To bring new theoretical insights into these questions, Monte Carlo simulations of AF signals were carried out in realistic models of the rat somatosensory cortex and olfactory bulb. We show that AF signals depend on the structural and physiological features of the brain area considered and are sensitive to changes in blood flow and volume induced by sensory activation. In addition, we demonstrate the feasibility of both NADHAF and Fp-AF in the olfactory bulb.
In Vivo Detection of Excitotoxicity by Manganese-enhanced MRI: Comparison with Physiological Stimulation
Manganese-enhanced MRI (MEMRI) is a powerful technique for the in vivo monitoring of brain function in animals. Manganese enters into cells through calcium channels, i.e., voltage-gated calcium channels and activated glutamate receptors (e.g., N-methyl-D-aspartate receptors). N-methyl-D-aspartate receptors are activated both in normal physiological and pathophysiological conditions. Consistent with these mechanisms, we showed that in the olfactory bulb, the MEMRI signal strongly increases when excitotoxic mechanisms are induced by an administration of a N-methyl-D-aspartate receptor agonist, quinolinate. We found that the intensity of the MEMRI signal in excitotoxic conditions is similar to the odor-evoked signal in normal physiological conditions. Finally, we showed that the dynamics of the MEMRI signal are determined by the early phase of manganese in the olfactory bulb. Overall, these data show that, in addition to physiological studies, MEMRI can be used as an in vivo method to follow-up the dynamics of excitotoxic events. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.
Alteration of Sensory-evoked Metabolic and Oscillatory Activities in the Olfactory Bulb of GLAST-deficient Mice
Astrocytes are key cellular elements in both the tripartite synapse and the neurovascular unit. To fulfill this dual role in synaptic activity and metabolism, they express a panel of receptors and transporters that sense glutamate. Among them, the GLT-1 and GLAST transporters are known to regulate extracellular glutamate concentrations at excitatory synapses and consequently modulate glutamate receptor signaling. These major uptake systems are also involved in energy supply to neurons. However, the functional role of GLAST in concurrent regulation of metabolic and neuronal activity is currently unknown. We took advantage of the attractive structural and functional features of the main olfactory bulb to explore the impact of GLAST on sensory information processing while probing both glutamate uptake and neuronal activity in glomeruli and deeper cellular layers, respectively. Using odor-evoked 2-deoxyglucose imaging and local field potential recordings in GLAST knockout mice, we show in vivo that deletion of GLAST alters both glucose uptake and neuronal oscillations in olfactory bulb networks.
Reconstruction of Field Excitatory Post-synaptic Potentials in the Dentate Gyrus from Amperometric Biosensor Signals
A new feasible and reproducible method to reconstruct local field potentials from amperometric biosensor signals is presented. It is based on the least-square fit of the current response of the biosensor electrode to a voltage step by the use of two time constants. After determination of the electrode impedance, Fast Fourier Transform (FFT) and Inverse FFT are performed to convert the recorded amperometric signals into voltage and trace the local field potentials using a resistor-capacitor circuit-based model. We applied this method to reconstruct field evoked potentials from currents recorded by a lactate biosensor in the rat dentate gyrus after stimulation of the perforant pathway in vivo. Initial slope of the reconstructed field excitatory postsynaptic potentials was used in order to demonstrate long term potentiation induced by high frequency stimulation of the perforant path. Our results show that reconstructing evoked potentials from amperometric recordings is a reliable method to obtain in vivo electrophysiological and amperometric information simultaneously from the same electrode in order to understand how chemical compounds vary with and modulate the dynamics of brain activity.
