One important characteristic of sensory input is frequency, with sensory neurons often tuned to narrow stimulus frequency ranges. Although vital for many neural computations, the cellular basis of such frequency tuning remains mostly unknown. In the electrosensory system of Apteronotus leptorhynchus, the primary processing of important environmental and communication signals occurs in pyramidal neurons of the electrosensory lateral line lobe. Spike trains transmitted by these cells can encode low-frequency prey stimuli with bursts of spikes and high-frequency communication signals with single spikes. Here, we demonstrate that the selective expression of SK2 channels in a subset of pyramidal neurons reduces their response to low-frequency stimuli by opposing their burst responses. Apamin block of the SK2 current in this subset of cells induced bursting and increased their response to low-frequency inputs. SK channel expression thus provides an intrinsic mechanism that predisposes a neuron to respond to higher frequencies and thus specific, behaviorally relevant stimuli.

In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis. However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients. Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.

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Calcium signals in vertebrate neurons can induce hyperpolarizing membrane responses through the activation of Ca(2+)-activated potassium channels. Of these, small conductance (SK) channels regulate neuronal responses through the generation of the medium after-hyperpolarization (mAHP). We have previously shown that an SK channel (AptSK2) contributes to signal processing in the electrosensory system of Apteronotus leptorhynchus. It was shown that for pyramidal neurons in the electrosensory lateral line lobe (ELL), AptSK2 expression selectively decreases responses to low-frequency signals. The localization of all the SK subunits throughout the brain of Apteronotus then became of substantial interest. We have now cloned two additional SK channel subunits from Apteronotus and determined the expression patterns of all three AptSK subunits throughout the brain. In situ hybridization experiments have revealed that, as in mammalian systems, the AptSK1 and 2 channels showed a partially overlapping expression pattern, whereas the AptSK3 channel was expressed in different brain areas. The AptSK1 and 2 channels were the primary subunits found in the major electrosensory processing areas. Immunohistochemistry further revealed distinct compartmentalization of the AptSK1 and 2 channels in the ELL. AptSK1 was localized to the apical dendrites of pyramidal neurons, whereas AptSK2 channels are primarily somatic. The distinct expression patterns of all three AptSK channels may reflect subtype-specific contributions to neuronal function, and the high homology between subtypes from a number of species suggests that the functional roles for each channel subtype are conserved from early vertebrate evolution.

The functional role of cholinergic input in the modulation of sensory responses was studied using a combination of in vivo and in vitro electrophysiology supplemented by mathematical modeling. The electrosensory system of weakly electric fish recognizes different environmental stimuli by their unique alteration of a self-generated electric field. Variations in the patterns of stimuli are primarily distinguished based on their frequency. Pyramidal neurons in the electrosensory lateral line lobe (ELL) are often tuned to respond to specific input frequencies. Alterations in the tuning of the pyramidal neurons may allow weakly electric fish to preferentially select for certain stimuli. Here we show that muscarinic receptor activation in vivo enhances the excitability, burst firing, and subsequently the response of pyramidal cells to naturalistic sensory input. Through a combination of in vitro electrophysiology and mathematical modeling, we reveal that this enhanced excitability and bursting likely results from the down-regulation of an A-type potassium current. Further, we provide an explanation of the mechanism by which these currents can mediate frequency tuning.