Neuroscience
-
Dementia, especially Alzheimer's disease, is a rapidly increasing medical condition that presents with enormous challenge for treatment. It is characterized by impairment in memory and cognitive function often accompanied by changes in synaptic transmission and plasticity in relevant brain regions such as the hippocampus. We recently synthesized TH-9, a conjugate racetam-methylxanthine compound and tested if it had potential for enhancing synaptic function and possibly, plasticity, by examining its effect on hippocampal fast excitatory synaptic transmission and plasticity. ⋯ Conversely, induction of LTP or LTD completely occluded the ability of TH-9 to enhance fEPSPs. Thus, TH-9 utilizes cholinergic and adenosinergic mechanisms to cause long-lasting enhancement in fEPSPs which were occluded by LTP and LTD. TH-9 may therefore employ similar or convergent mechanisms with frequency-dependent synaptic plasticities to produce the observed long-lasting enhancement in synaptic transmission and may thus, have potential for use in improving memory.
-
Persistent inflammation is associated with a shift in spinal GABA(A) signaling from inhibition to excitation such that GABA(A)-receptor activation contributes to inflammatory hyperalgesia. We tested the hypothesis that the primary afferent is the site of the persistent inflammation-induced shift in GABA(A) signaling which is due to a Na(+)-K(+)-Cl(-)-co-transporter (NKCC1)-dependent depolarization of the GABA(A) current equilibrium potential (E(GABA)). Acutely dissociated retrogradely labeled cutaneous dorsal root ganglion (DRG) neurons from naïve and inflamed (3 days after a subcutaneous injection of complete Freund's adjuvant) adult male rats were studied with Ca(2+) imaging, western blot and gramicidin-perforated patch recording. ⋯ Furthermore, the increase in excitatory response was comparable in both HEPES- and HCO(3)(-)-buffered solutions, but was only associated with a depolarization of E(GABA) in HCO(3)(-)-based solution. In contrast, under both recording conditions, the excitatory response was associated with an increase in GABA(A) current density, a decrease in low threshold K(+) current density, and resting membrane potential depolarization. Our results suggest that increasing K(+) conductance in afferents innervating a site of persistent inflammation may have greater efficacy in the inhibition of inflammatory hyperalgesia than attempting to drive a hyperpolarizing shift in E(GABA).
-
The hippocampus plays a critical role in contextual fear conditioning. Population activity in the hippocampal CA1 encoding the surrounding environment is thought to be responsible for retrieval of contextual fear memory. However, the characteristics of CA1 neuronal ensemble activity during retrieval of contextual fear memory remain unclear. ⋯ In the Shock group, exposure to the same conditioning chamber twice activated a similarly overlapping neuronal population as exposure to two different chambers, with overlap smaller than in nonshocked mice exposed to the same chamber twice. Thus, population activity in the hippocampal CA1 encoding the surrounding environment is detected during spatial exploration, but absent during contextual fear memory expression. Even the variable ensemble activity of CA1 may contribute to retrieval of contextual fear memory.
-
Purinergic signaling through activation of P2X and P2Y receptors is critically important in the chemical senses. In the mouse main olfactory epithelium (MOE), adenosine 5'-triphosphate (ATP) elicits an increase in intracellular calcium ([Ca(2+)](I)) and reduces the responsiveness of olfactory sensory neurons to odorants through activation of P2X and P2Y receptors. We investigated the role of purinergic signaling in vomeronasal sensory neuron (VSN)s from the mouse vomeronasal organ (VNO), an olfactory organ distinct from the MOE that responds to many conspecific chemical cues. ⋯ Mechanical stimulation of the VNO induced the release of ATP, detected by luciferin-luciferase luminometry, and this release of ATP was completely abolished in the presence of the connexin/pannexin hemichannel blocker, carbenoxolone. We conclude that the release of ATP could occur during the activity of the vasomotor pump that facilitates the movement of chemicals into the VNO for detection by VSNs. This mechanism could lead to a global increase in excitability and the chemosensory response in VSNs through activation of P2X receptors.
-
Signal detection theory (SDT) provides a framework for interpreting psychophysical experiments, separating the putative internal sensory representation and the decision process. SDT was used to analyse ferret behavioural responses in a (yes-no) tone-in-noise detection task. Instead of measuring the receiver-operating characteristic (ROC), we tested SDT by comparing responses collected using two common psychophysical data collection methods. ⋯ The data suggest trial-by-trial reward-driven optimization of the decision process. Understanding the factors determining behavioural responses is important for correlating neural activity and behaviour. SDT provides a good account of animal psychoacoustics, and can be validated using standard psychophysical methods and computer simulations, without recourse to ROC measurements.