Weakly electric fish use electroreception for both active and passive electrolocation and for electrocommunication. While both active and passive electrolocation systems are prominent in weakly electric Mormyriform fishes, knowledge of their passive electrolocation ability is still scarce. To better estimate the contribution of passive electric sensing to the orientation toward electric stimuli in weakly electric fishes, we investigated frequency tuning applying classical input-output characterization and stimulus reconstruction methods to reveal the encoding capabilities of ampullary receptor afferents. Ampullary receptor afferents were most sensitive (threshold: 40 μV/cm) at low frequencies (<10 Hz) and appear to be tuned to a mix of amplitude and slope of the input signals. The low-frequency tuning was corroborated by behavioral experiments, but behavioral thresholds were one order of magnitude higher. The integration of simultaneously recorded afferents of similar frequency-tuning resulted in strongly enhanced signal-to-noise ratios and increased mutual information rates but did not increase the range of frequencies detectable by the system. Theoretically the neuronal integration of input from receptors experiencing opposite polarities of a stimulus (left and right side of the fish) was shown to enhance encoding of such stimuli, including an increase of bandwidth. Covariance and coherence analysis showed that spiking of ampullary afferents is sufficiently explained by the spike-triggered average, i.e., receptors respond to a single linear feature of the stimulus. Our data support the notion of a division of labor of the active and passive electrosensory systems in weakly electric fishes based on frequency tuning. Future experiments will address the role of central convergence of ampullary input that we expect to lead to higher sensitivity and encoding power of the system.

The neuropeptide S system has been implicated in a number of centrally mediated behaviors including memory consolidation, anxiolysis, and increased locomotor activity. Characterization of these behaviors has been primarily accomplished using the endogenous 20AA peptide (NPS) that demonstrates relatively equal potency for the calcium mobilization and cAMP second messenger pathways at human and rodent NPS receptors. This study is the first to demonstrate that truncations of the NPS peptide provides small fragments that retain significant potency only at one of two single polymorphism variants known to alter NPSR function (NPSR-107I), yet demonstrate a strong level of bias for the calcium mobilization pathway over the cAMP pathway. We have also determined that the length of the truncated peptide correlates with the degree of bias for the calcium mobilization pathway. A modified tetrapeptide analog (4) has greatly attenuated hyperlocomotor stimulation in vivo but retains activity in assays that correlate with memory consolidation and anxiolytic activity. Analog 4 also has a bias for the calcium mobilization pathway, at the human and mouse receptor. This suggests that future agonist ligands for the NPS receptor having a bias for calcium mobilization over cAMP production will function as non-stimulatory anxiolytics that augment memory formation.

The lateral fluid percussion injury (FPI) model is well established and has been used to study TBI and post-traumatic epilepsy (PTE). However, considerable variability has been reported for the specific parameters used in different studies that have employed this model, making it difficult to harmonize and interpret the results between laboratories. For example, variability has been reported regarding the size and location of the craniectomy, how the Luer lock hub is placed relative to the craniectomy, the atmospheric pressure applied to the dura and the duration of the pressure pulse. Each of these parameters can impact injury severity, which directly correlates with the incidence of PTE. This has been manifested as a wide range of mortality rates, righting reflex times and incidence of convulsive seizures reported. Here we provide a detailed protocol for the method we have used to help facilitate harmonization between studies. We used FPI in combination with a wireless EEG telemetry system to continuously monitor for electrographic changes and detect seizure activity. FPI is induced by creating a 5 mm craniectomy over the left hemisphere, between the Bregma and Lambda and adjacent to the lateral ridge. A Luer lock hub is secured onto the skull over the craniectomy. This hub is connected to the FPI device, and a 20-millisecond pressure pulse is delivered directly to the intact dura through pressure tubing connected to the hub via a twist lock connector. Following recovery, rats are re-anesthetized to remove the hub. Five 0.5 mm, stainless steel EEG electrode screws are placed in contact with the dura through the skull and serve as four recording electrodes and one reference electrode. The electrode wires are collected into a pedestal connector which is secured into place with bone cement. Continuous video/EEG recordings are collected for up to 4 weeks post TBI.

The lateral fluid percussion injury (FPI) model is well established and has been used to study TBI and post-traumatic epilepsy (PTE). However, considerable variability has been reported for the specific parameters used in different studies that have employed this model, making it difficult to harmonize and interpret the results between laboratories. For example, variability has been reported regarding the size and location of the craniectomy, how the Luer lock hub is placed relative to the craniectomy, the atmospheric pressure applied to the dura and the duration of the pressure pulse. Each of these parameters can impact injury severity, which directly correlates with the incidence of PTE. This has been manifested as a wide range of mortality rates, righting reflex times and incidence of convulsive seizures reported. Here we provide a detailed protocol for the method we have used to help facilitate harmonization between studies. We used FPI in combination with a wireless EEG telemetry system to continuously monitor for electrographic changes and detect seizure activity. FPI is induced by creating a 5 mm craniectomy over the left hemisphere, between the Bregma and Lambda and adjacent to the lateral ridge. A Luer lock hub is secured onto the skull over the craniectomy. This hub is connected to the FPI device, and a 20-millisecond pressure pulse is delivered directly to the intact dura through pressure tubing connected to the hub via a twist lock connector. Following recovery, rats are re-anesthetized to remove the hub. Five 0.5 mm, stainless steel EEG electrode screws are placed in contact with the dura through the skull and serve as four recording electrodes and one reference electrode. The electrode wires are collected into a pedestal connector which is secured into place with bone cement. Continuous video/EEG recordings are collected for up to 4 weeks post TBI. Video LinkThe video component of this article can be found at https://www.jove.com/video/59637/ 5 . Importantly, chronic, recurrent seizures that occur as a consequence of TBI are often pharmacoresistant, increasing the burden of the disease 6 . The exact mechanisms that lead to post-traumatic epilepsy (PTE) remain unclear. However, several key epidemiology studies have examined the incidence and potential risk of developing post-traumatic epilepsy (PTE)

Opiate abuse is a worldwide epidemic that costs nations billions of dollars to treat. Rewarding effects of opioids and other drugs of abuse are partially reliant on the activity of dopaminergic neurons located in reward centers of the brain such as the ventral tegmental area (VTA). The VTA receives cholinergic input from only two sources, the pedunculopontine tegmentum (PPTg) and the laterodorsal tegmentum (LDTg). Excitotoxic lesions to the PPTg in rats have previously been shown to reduce the rewarding effect of opiates (Bechara & van der Kooy, 1989; Olmstead & Franklin, 1997; Parker & van der Kooy, 1995). These studies were unable to identify the specific neuronal subtype responsible for the reduced rewarding effect, though they suggested the cholinergic neurons were responsible. By using a diphtheria‐UII fusion toxin to selectively ablate cholinergic neurons in the PPTg and LDTg we were able to test the role of cholinergic projections to the VTA. The toxin was injected bilaterally into the PPTg, LDTg, or VTA of male Sprague‐Dawley rats through stereotaxic surgery. Injection into the VTA creates a retrograde lesion that specifically ablates the cholinergic neurons of the PPTg and LDTg that innervate the VTA.The animals were subjected to an acoustic startle reflex/pre‐pulse inhibition paradigm in weeks 4, 8, and 10 post‐surgery. Animals with cholinergic depletion in the PPTg were unable to startle to the point where pre‐pulse inhibition was unable to be measured. While not significant, there was a trend toward an increase in startle in animals that received a VTA retrograde lesion. These findings suggest that the cholinergic PPTg is necessary for integrating sensory processing and motor output. Cholinergic input to the VTA from both the PPTg and LDTg produced a novel effect. Ten weeks post‐surgery the rats were subjected to a morphine conditioned place preference paradigm (CPP), an extinction period, and then a cocaine CPP paradigm. Animals with lesions to the LDTg were able to form cocaine‐mediated CPP but not morphine‐mediated CPP. PPTg lesioned animals formed preference for both morphine and cocaine. Sham animals and the VTA retrograde animals also formed preference for both drugs. These findings suggest that cholinergic neurons in the LDTg that project to an area that is not the VTA likely play a role in morphine‐related reward, and that the cholinergic output from the PPTg is not required in the formation of morphine conditioned place preference. Taking the results of both experiments together, it can be inferred that the cholinergic LDTg plays a role in reward while the cholinergic PPTg plays a role in sensory processing. It is likely that these two areas work in concert to modulate a variety of behaviors. While these findings don't provide a treatment for opiate abuse, they help to further our understanding of the neuronal mechanisms that drive drug addiction.Support or Funding InformationR00DA024754This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.