Minocycline Protects Structure But Not Function after Nerve Injury
Travis M. Rotterman, Violet V. Garcia, Stephen N. Housley, Paul Nardelli, Rommy Sierra, et al.
(see pages 4390–4404)
Peripheral nerves severed by injury can regenerate, but often function does not fully recover, leading to motor behavioral deficits like stretch areflexia (the loss of stretch reflex) and gait ataxia, or poorly controlled walking. These deficits result from the loss of synaptic connections between Ia afferent sensory neurons and motoneurons in the spinal cord, which is mediated by immune cells (microglia). To investigate the effects of an anti-inflammatory agent on recovery after peripheral nerve injury in rats, Rotterman et al. surgically cut and immediately rejoined the ends of the medial gastrocnemius (MG) nerve of rats that received minocycline (or a vehicle control) for 2 weeks. In vehicle-treated rats, MG motoneurons underwent synapse loss from the soma, which was visualized by the presence of the vesicular glutamate transporter VGluT1; that loss was prevented in rats that received minocycline. The synaptic rescue by 2 weeks of minocycline treatment was preserved for as long as 6 months, whereas in untreated rats, neurons continued to undergo synapse loss. The authors assessed motor recovery by injecting current into motoneurons and measuring the elicited muscle contraction. To assess sensory recovery, they used vibration stimulation of the tendon and measured firing in the sensory neurons, which were mostly proprioceptive Ia afferents. Sensory nerve responses could not be elicited at 3 months, but at 6 months the afferents could encode responses to vibration. Motor recovery happened faster, by 3 months. In uninjured rats, tendon vibration resulted in 100% of motoneurons firing in response, but in nerve-injured rats only 38% of neurons fired in response to vibration. Rats that received minocycline following nerve injury did not fare better; the response rate fell to 22%, even though synapses were structurally intact. The amplitude of those potentials in both vehicle-treated and minocycline-treated rats was smaller than those in uninjured rats. When the researchers elicited a reflex movement, 96% of control rats responded with muscle contraction, with only one detectable response among the nerve-injured rats. Together, the findings indicate that, despite preserving the structural integrity of afferent–motoneuron synapses in the spinal cord, minocycline treatment did not rescue sensory motor function after peripheral nerve injury.
Neurolucida reconstruction from confocal image stacks of a motoneuron with VGlut1-expressing synapses (white) from an uninjured rat.
Echolocators Use “Visual” Brain Areas in Spatial Navigation, Too
Liam J. Norman and Lore Thaler
(see pages 4470–4486)
Research over the past decade has revealed complex brain networks that allow humans to visually navigate through the world. But are those circuits specifically equipped to encode visual stimuli, or could they aid in navigation using any sensory modality? Norman and Thaler set out to answer that question this week in a brain-imaging study of a unique population of people: blind expert echolocators (EEs), who make clicking noises with their mouth and derive information about their surroundings from the returning sounds. The researchers used functional magnetic resonance imaging to focus on the occipital place area (OPA), which has previously been shown to guide navigation by providing boundary information, as well as the associated parahippocampal place area and superior parietal lobule. Six EE participants, 12 blind control (BC) participants, and 14 sighted control (SC) participants underwent scanning while they listened to echolocation sounds conveying a coherent route, scrambled versions of echolocation sounds, or nonecho sounds. EEs were significantly more accurate than BCs or SCs at decoding a navigation route from the echolocation sounds and at distinguishing the actual and scrambled echoes. All groups easily distinguished echo from nonecho sounds. When comparing the route echo to scrambled echo sounds, EEs showed a greater response in the OPA, but other brain areas did not differ between groups. The data show that echolocators had unique responses to echo sounds compared with other groups, and that they used the OPA for spatial navigation processing. The work supports other recent research, suggesting that the brain is not organized in a rigid way based on sensory modality, but rather may be more flexibly organized to perform a given task using multiple modalities.
Footnotes
This Week in The Journal was written by Stephani Sutherland
