Neuronal Death in the Contralateral Un-Injured Retina after Unilateral Axotomy: Role of Microglial Cells

For years it has been known that unilateral optic nerve lesions induce a bilateral response that causes an inflammatory and microglial response in the contralateral un-injured retinas. Whether this contralateral response involves retinal ganglion cell (RGC) loss is still unknown. We have analyzed the population of RGCs and the expression of several genes in both retinas of pigmented mice after a unilateral axotomy performed close to the optic nerve head (0.5 mm), or the furthest away that the optic nerve can be accessed intraorbitally in mice (2 mm). In both retinas, RGC-specific genes were down-regulated, whereas caspase 3 was up-regulated. In the contralateral retinas, there was a significant loss of 15% of RGCs that did not progress further and that occurred earlier when the axotomy was performed at 2 mm, that is, closer to the contralateral retina. Finally, the systemic treatment with minocycline, a tetracycline antibiotic that selectively inhibits microglial cells, or with meloxicam, a non-steroidal anti-inflammatory drug, rescued RGCs in the contralateral but not in the injured retina. In conclusion, a unilateral optic nerve axotomy triggers a bilateral response that kills RGCs in the un-injured retina, a death that is controlled by anti-inflammatory and anti-microglial treatments. Thus, contralateral retinas should not be used as controls.

Fish prey change strategy with the direction of a threat

Predation is a fundamental interaction between species, yet it is unclear what escape strategies are effective for prey survival. Classical theory proposes that prey should either escape in a direction that conforms to a performance optimum or that is random and therefore unpredictable. Here, we show that larval zebrafish ( Danio rerio ) instead use a mixed strategy that may be either random or directed. This was determined by testing classic theory with measurements of the escape direction in response to a predator robot. We found that prey consistently escaped in a direction contralateral to the robot when approached from the side of the prey's body. At such an orientation, the predator appeared in the prey's central visual field and the contralateral response was consistent with a model of strategy that maximizes the distance from the predator. By contrast, when the robot approached the rostral or caudal ends of the body, and appeared in the prey's peripheral vision, the escape showed an equal probability of a contralateral or ipsilateral direction. At this orientation, a contralateral response offered little strategic advantage. Therefore, zebrafish larvae adopt an escape strategy that maximizes distance from the threat when strategically beneficial and that is otherwise random. This sensory-mediated mixed strategy may be employed by a diversity of animals and offers a new paradigm for understanding the factors that govern prey survival.

Air-Conduction Auditory Steady-State Response: Comparison of Interchannel Recording Using Two Modulation Frequencies

Background: Two-channel auditory steady-state response (ASSR) recording at high and low MF (modulation frequency) most likely provides an insight about the response amplitude and latency from different directions at the brainstem level and at the thalamus or cortical level. Little is known about the combined relationship between MF (39 and 79 Hz) and electrode montages (ipsilateral and contralateral) to single AM (amplitude modulation) tones on the ASSR amplitude and latency. Purpose: To determine if ipsilateral versus contralateral response asymmetries are present at the brainstem level (79 Hz ASSR) and at the thalamus or cortical levels (39 Hz ASSR). Research Design: Descriptive and inferential statistics for interchannel ipsilateral and contralateral ASSR amplitude and latency to 79 and 39 Hz. Study Sample: Twenty-five normal-hearing, right-handed young female adults participated in the study. All participants were right-handed, and their age ranged between 18 to 28 years (mean 24.5 ± 1.6 years). Data Collection and Analysis: Ipsilateral and contralateral ASSR to 39 and 79 Hz MF and 100% AM stimuli were recorded at 500, 2000, and 4000 Hz carrier frequencies at 65 dB SPL. The ASSR amplitudes and phases were determined for each MF across Fc (carrier frequency) for the two channels to the test (right) ear. ASSR amplitude and latency between recording montages for each MF and across carrier frequency were compared by computing two-way repeated measures ANOVA. Results: The mean ipsilateral ASSR amplitudes to 39 Hz across frequency were slightly larger (228.6 ± 61.6 µV) than the contralateral response amplitude (223.2 ± 78 µV) while the mean ipsilateral 79 Hz amplitudes were smaller (127.3 ± 114.8) compared to contralateral 79 Hz amplitude (154.6 ± 112.7 µV). For latency response, the mean ipsilateral/contralateral latency difference, on average, was 1 msec or less for both MFs. Results, in normal female adults, indicated no significant interchannel ASSR asymmetries for amplitude and latency (p > 0.05) at the brainstem (79 Hz ASSR) and at the thalamus or cortical levels (39 Hz ASSR). Conclusions: Interchannel ipsilateral and contralateral ASSR amplitude and latency to 79 and 39 Hz are not significantly different in normal, young female adults. Two-channel recording of ASSR to different MFs may be of clinical value in otoneurologic assessment.

Response Properties of Single Units in the Dorsal Nucleus of the Lateral Lemniscus of Decerebrate Cats

The dorsal nucleus of the lateral lemniscus (DNLL) receives afferent inputs from many brain stem nuclei and, in turn, is a major source of inhibitory inputs to the inferior colliculus (IC). The goal of this study was to characterize the monaural and binaural response properties of neurons in the DNLL of unanesthetized decerebrate cat. Monaural responses were classified according to the patterns of excitation and inhibition observed in contralateral and ipsilateral frequency response maps. Binaural classification was based on unit sensitivity to interaural level differences. The results show that units in the DNLL can be grouped into three distinct types. Type v units produce contralateral response maps that show a wide V-shaped excitatory area and no inhibition. These units receive ipsilateral excitation and exhibit binaural facilitation. The contralateral maps of type i units show a more restricted I-shaped region of excitation that is flanked by inhibition. Type o maps display an O-shaped island of excitation at low stimulus levels that is bounded by inhibition at higher levels. Both type i and type o units receive ipsilateral inhibition and exhibit binaural inhibition. Units that produce type v maps have a low best frequency (BF), whereas type i and type o units have high BFs. Type v and type i units give monotonic rate-level responses for both BF tones and broadband noise. Type o units are inhibited by tones at high levels, but are excited by high-level noise. These results show that the DNLL can exert strong, differential effects in the IC.

Attenuation of phrenic motor discharge by phrenic nerve afferents

Short latency phrenic motor responses to phrenic nerve stimulation were studied in anesthetized, paralyzed cats. Electrical stimulation (0.2 ms, 0.01–10 mA, 2 Hz) of the right C5 phrenic rootlet during inspiration consistently elicited a transient reduction in the phrenic motor discharge. This attenuation occurred bilaterally with an onset latency of 8–12 ms and a duration of 8–30 ms. Section of the ipsilateral C4-C6 dorsal roots abolished the response to stimulation, thereby confirming the involvement of phrenic nerve afferent activity. Stimulation of the left C5 phrenic rootlet or the right thoracic phrenic nerve usually elicited similar inhibitory responses. The difference in onset latency of responses to cervical vs. thoracic phrenic nerve stimulation indicates activation of group III afferents with a peripheral conduction velocity of approximately 10 m/s. A much shorter latency response (5 ms) was evoked ipsilaterally by thoracic phrenic nerve stimulation. Section of either the C5 or C6 dorsal root altered the ipsilateral response so that it resembled the longer latency contralateral response. The low-stimulus threshold and short latency for the ipsilateral response to thoracic phrenic nerve stimulation suggest that it involves larger diameter fibers. Decerebration, decerebellation, and transection of the dorsal columns at C2 do not abolish the inhibitory phrenic-to-phrenic reflex.