25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Sonic hedgehog delivery from self-assembled nanofiber hydrogels reduces the fibrotic response in models of erectile dysfunction

Erectile dysfunction (ED) is a serious medical condition in which current treatments are ineffective in prostatectomy and diabetic patients, due to injury to the cavernous nerve (CN), which causes irreversible remodeling of the penis (decreased smooth muscle and increased collagen), through a largely undefined mechanism. We propose that sonic hedgehog (SHH) and neural innervation, are indispensable regulators of collagen in the penis, with decreased SHH protein being an integral component of the fibrotic response to loss of innervation. We examined collagen abundance and morphology in control (Peyronie’s), prostatectomy and diabetic patients, and in rat models of penile development, CN injury, SHH inhibition and under regenerative conditions, utilizing self-assembling peptide amphiphile (PA) nanofiber hydrogels for SHH delivery. Collagen abundance increased in penis of ED patients. In rats, collagen increased with CN injury in a defined time frame independent of injury severity. An inverse relationship between SHH and collagen abundance was identified; SHH inhibition increased and SHH treatment decreased penile collagen. SHH signaling in the pelvic ganglia (PG)/CN is important to maintain CN integrity and when inhibited, downstream collagen induction occurs. Collagen increased throughout penile development and with age, which is important when considering how to treat fibrosis clinically. These studies show that SHH PA treatment reduces collagen under regenerative post-prostatectomy conditions, indicating broad application for ED prevention in prostatectomy, diabetic and aging patients and in other peripheral nerve injuries. The PA nanofiber protein vehicle may be widely applicable as an in vivo delivery tool

MRI vs Transrectal Ultrasound to Estimate Prostate Volume and PSAD: Impact on Prostate Cancer Detection.

OBJECTIVES: To compare multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound (TRUS) to estimate prostate volume and prostate specific antigen density (PSAD) as well as subsequent impact on prostate cancer (PCa) detection. METHODS: Patients referred for mpMRI prior to mpMRI-TRUS fusion-guided prostate biopsy between 2015 and 2020 were identified. Volume and calculated PSAD by mpMRI and TRUS were compared. Associations with presence of any PCa and clinically significant PCa (csPCa; Gleason ≥3 + 4) were evaluated using linear regression (interaction by volume quartile), logistic regression, and receiver operating characteristics. RESULTS: Among 640 men, TRUS underestimated prostate volume relative to mpMRI (median 49.2cc vs. 54.1cc) with 8% lower volume per cc up to 77.5cc (First-third quartile) and 39% lower volume per additional cc above 77.5cc (fourth quartile). For men undergoing radical prostatectomy, mpMRI had a higher correlation coefficient relative to TRUS (0.913 vs 0.878) when compared to surgical pathology. mpMRI PSAD had slightly higher odds vs TRUS PSAD for detecting any PCa (OR 2.94 and OR 2.78, both P CONCLUSION: TRUS underestimates prostate volume relative to mpMRI. PSAD based on mpMRI may be better associated with detection of PCa compared to TRUS, but utility of PSAD may be limited for larger prostates