How did humans learn to walk? New evolutionary study offers an earful

Humans and our closest relatives, living apes, display a remarkable diversity of types of locomotion -- from walking upright on two legs to climbing in trees and walking using all four limbs.

While scientists have long been intrigued by the question of how humans' bipedal stance and movement evolved from a quadrupedal ancestor, neither past studies nor fossil records have permitted the reconstruction of a clear and definitive history of the early evolutionary stages that led to human bipedalism.

However, a new study, which centers on recently discovered evidence from skulls of a 6-million-year-old fossil ape, Lufengpithecus, offers important clues about the origins of bipedal locomotion courtesy of a novel method: analyzing its bony inner ear region using three-dimensional CT-scanning.

"The semicircular canals, located in the skull between our brains and the external ear, are critical to providing our sense of balance and position when we move, and they provide a fundamental component of our locomotion that most people are probably unaware of," explains Yinan Zhang, a doctoral student at the Institute of Vertebrate Paleontology and Paleoanthropology of the Chinese Academy of Sciences (IVPP) and the lead author of the paper, which appears in the journal the Innovation. "The size and shape of the semicircular canals correlate with how mammals, including apes and humans, move around their environment. Using modern imaging technologies, we were able to visualize the internal structure of fossil skulls and study the anatomical details of the semicircular canals to reveal how extinct mammals moved."

"Our study points to a three-step evolution of human bipedalism," adds Terry Harrison, a New York University anthropologist and one of the paper's co-authors.

"First, the earliest apes moved in the trees in a style that was most similar to aspects of the way that gibbons in Asia do today. Second, the last common ancestor of apes and humans was similar in its locomotor repertoire to Lufengpithecus, using a combination of climbing and clambering, forelimb suspension, arboreal bipedalism, and terrestrial quadrupedalism. It is from this broad ancestral locomotor repertoire that human bipedalism evolved."

Most studies of the evolution of ape locomotion had focused on comparisons of the bones of the limbs, shoulders, pelvis, and spine and the way they are associated with the different types of locomotor behaviors seen in living apes and humans.

However, the diversity of locomotor behaviors in living apes and the incompleteness of the fossil record have hampered the development of a clear picture of human bipedalism's origins.

The skulls of Lufengpithecus -- originally discovered in China's Yunnan Province in the early 1980s -- have given scientists the opportunity to address, in new ways, unanswered questions about the evolution of locomotion.

However, the heavy compression and distortion of the skulls obscured the bony ear region and led previous researchers to believe that the delicate semicircular canals were not preserved.

To better explore this region, Zhang, Ni and Harrison, along with other researchers at IVPP and the Yunnan Institute of Cultural Relics and Archaeology (YICRA), used three dimensional scanning technologies to illuminate these portions of the skulls to create a virtual reconstruction of the inner ear's bony canals.

They then compared these scans to those collected from other living and fossil apes and humans from Asia, Europe, and Africa.

"Our analyses show that early apes shared a locomotor repertoire that was ancestral to human bipedalism," explains IVPP Professor Xijun Ni, who led the project.

"It appears that the inner ear provides a unique record of the evolutionary history of ape locomotion that offers an invaluable alternative to the study of the postcranial skeleton."

"Most fossil apes and their inferred ancestors are intermediate in locomotor mode between gibbons and African apes," adds Ni. "Later, the human lineage diverged from the great apes with the acquisition of bipedalism, as seen in Australopithecus, an early human relative from Africa."

By studying the rate of evolutionary change in the bony labyrinth, the international team proposed that climate change may have been an important environmental catalyst in promoting the locomotor diversification of apes and humans.

Read more at Science Daily

An unexpected doorway into the ear opens new possibilities for hearing restoration

An international team of researchers has developed a new method to deliver drugs into the inner ear. The discovery was possible by harnessing the natural flow of fluids in the brain and employing a little understood backdoor into the cochlea. When combined to deliver a gene therapy that repairs inner ear hair cells, the researchers were able to restore hearing in deaf mice.

"These findings demonstrate that cerebrospinal fluid transport comprises an accessible route for gene delivery to the adult inner ear and may represent an important step towards using gene therapy to restore hearing in humans," said Maiken Nedergaard, MD, DMSc, senior author of the new study, which appears in the journal Science Translational Medicine.

Nedergaard is co-director of the Center for Translational Neuromedicine at University of Rochester and the University of Copenhagen. The study was the product of a collaboration between researchers at the two universities and a group led by Barbara Canlon, Ph.D. in the Laboratory of Experimental Audiology at the Karolinska Institute in Stockholm, Sweden.

The number of people worldwide predicted to have mild to complete hearing loss is expected to grow to around 2.5 billion by mid-century. The primarily cause is the death or loss of function of hair cells found in the cochlea -- which are responsible for relaying sounds to the brain -- due to mutations of critical genes, aging, noise exposure, and other factors.

While hair cells do not naturally regenerated in humans and other mammals, gene therapies have shown promise and in separate studies have successfully repaired the function of hair cells in neo-natal and very young mice. However, as both mice and humans age, the cochlea, already a delicate structure, becomes enclosed in temporal bone. At this point, any effort to reach the cochlea and deliver a gene therapy via surgery risks damaging this sensitive area and altering hearing.

In the new study, the researchers describe a little understood passage into the cochlea called the cochlear aqueduct. While the name conjures images of monumental stone architecture, the cochlear aqueduct is thin boney channel no larger than a single strand of hair. Suspected to play a role in balancing pressure in the ear, new study shows that that the cochlear aqueduct also acts as a conduit between the cerebrospinal fluid found in the inner ear and the rest of the brain.

Scientists are developing clearer picture of the mechanics of glymphatic system, the brain's unique process of removing waste first described by the Nedergaard lab in 2012. Because the glymphatic system pumps cerebrospinal fluid deep into brain tissue to wash away toxic proteins, researchers have been eyeing it as a potentially new way to deliver drugs into the brain, a major challenge in developing drugs for neurological disorders.

Researchers have also discovered that the complex movement of fluids driven by the glymphatic system extend to the eyes and the peripheral nervous system, including ear. The new study represented an opportunity to put the drug delivery potential of the glymphatic system to the test, while at the same time targeting a previously unreachable part of the auditory system.

Employing a number of imagining and modeling technologies, the researchers were able to develop a detailed portrait of how fluid from other parts of the brain flows through cochlear aqueduct and into the inner ear. The team then injected an adeno-associated virus into the cisterna magna, a large reservoir of cerebrospinal fluid found at the base of the skull. The virus found its way into the inner ear via the cochlear aqueduct, delivered a gene therapy that expresses a protein called vesicular glutamate transporter-3, which enable the hair cells to transmit signal and rescued hearing in adult deaf mice.

"This new delivery route into the ear may not only serve the advancement of auditory research, but also prove useful when translated to humans with progressive genetic-mediated hearing loss," said Nedergaard.

Read more at Science Daily

Oldest spinosaur brains revealed

Researchers from the University of Southampton and Ohio University have reconstructed the brains and inner ears of two British spinosaurs, helping uncover how these large predatory dinosaurs interacted with their environment.

Spinosaurs are an unusual group of theropod dinosaurs, equipped with long, crocodile-like jaws and conical teeth. These adaptations helped them live a somewhat-aquatic lifestyle that involved stalking riverbanks in quest of prey, among which were large fish. This way of life was very different from that of more familiar theropods, like Allosaurus and Tyrannosaurus.

To better understand the evolution of spinosaur brains and senses, the team scanned fossils of Baryonyx from Surrey and Ceratosuchops from the Isle of Wight. These two are the oldest spinosaurs for which braincase material is known. The huge creatures would have been roaming the planet about 125 million years ago years ago. The braincases of both specimens are well preserved, and the team digitally reconstructed the internal soft tissues that had long rotted away.

The researchers found the olfactory bulbs, which process smells, weren't particularly developed, and the ear was probably attuned to low frequency sounds. Those parts of the brain involved in keeping the head stable and the gaze fixed on prey were possibly less developed than they were in later, more specialised spinosaurs.

Findings are due to be published in the Journal of Anatomy.

"Despite their unusual ecology, it seems the brains and senses of these early spinosaurs retained many aspects in common with other large-bodied theropods -- there is no evidence that their semi-aquatic lifestyles are reflected in the way their brains are organised," said University of Southampton PhD student Chris Barker, who led the study.

One interpretation of this evidence is that the theropod ancestors of spinosaurs already possessed brains and sensory adaptations suited for part-time fish catching, and that 'all' spinosaurs needed to do to become specialised for a semi-aquatic existence was evolve an unusual snout and teeth.

"Because the skulls of all spinosaurs are so specialised for fish-catching, it's surprising to see such 'non-specialised' brains," said contributing author Dr Darren Naish. "But the results are still significant. It's exciting to get so much information on sensory abilities -- on hearing, sense of smell, balance and so on -- from British dinosaurs. Using cutting-edged technology, we basically obtained all the brain-related information we possibly could from these fossils," Dr Naish said.

Over the last few years, the EvoPalaeo Lab at the University of Southampton has conducted substantial research on new spinosaurs from the Isle of Wight. Ceratosuchops itself was only announced by the team in 2021, and its discovery was followed up by the publication of another new spinosaur -- the gigantic White Rock spinosaur -- in 2022. The braincase of Ceratosuchops was scanned at the ?-Vis X-ray Imaging Centre at the University of Southampton, home to some of the most powerful CT scanners in the country, and a model of its brain will be on display alongside its bones at Dinosaur Isle Museum in Sandown, on the Isle of Wight.

"This new research is just the latest in what amounts to a revolution in palaeontology due to advances in CT-based imaging of fossils," said co-author Lawrence M. Witmer, professor of anatomy at the Ohio University Heritage College of Osteopathic Medicine, who has been CT scanning dinosaurs -- including Baryonyx -- for over 25 years. "We're now in a position to be able to assess the cognitive and sensory capabilities of extinct animals and explore how the brain evolved in behaviourally extreme dinosaurs like spinosaurs."

Read more at Science Daily

Inner ear has a need for speed

The sensory organs that allow us to walk, dance and turn our heads without dizziness or loss of balance contain specialized synapses that process signals faster than any other in the human body.

In a discovery more than 15 years in the making, a small group of neuroscientists, physicists and engineers from several institutions has unlocked the mechanism of the synapses, paving the way for research that could improve treatments for vertigo and balance disorders that affect as many as 1 in 3 Americans over age 40.

The new study in the Proceedings of the National Academy of Sciences describes the workings of "vestibular hair cell-calyx synapses," which are found in organs of the innermost ear that sense head position and movements in different directions.

"Nobody fully understood how this synapse can be so fast, but we have shed light on the mystery," said Rob Raphael, a Rice University bioengineer who co-authored the study with the University of Chicago's Ruth Anne Eatock, the University of Illinois Chicago's Anna Lysakowski, current Rice graduate student Aravind Chenrayan Govindaraju and former Rice graduate student Imran Quraishi, now an assistant professor at Yale University.

Synapses are biological junctions where neurons can relay information to one another and other parts of the body. The human body contains hundreds of trillions of synapses, and almost all of them share information via quantal transmission, a form of chemical signaling via neurotransmitters that requires at least 0.5 milliseconds to send information across a synapse.

Prior experiments had shown a faster, "nonquantal" form of transmission occurs in vestibular hair cell-calyx synapses, the points where motion-sensing vestibular hair cells meet afferent neurons that connect directly to the brain. The new research explains how these synapses operate so quickly.

In each, a signal-receiving neuron surrounds the end of its partner hair cell with a large cuplike structure called a calyx. The calyx and hair cell remain separated by a tiny gap, or cleft, measuring just a few billionths of a meter.

"The vestibular calyx is a wonder of nature," Lysakowski said. "Its large cup-shaped structure is the only one of its kind in the entire nervous system. Structure and function are intimately related, and nature obviously devoted a great deal of energy to produce this structure. We've been trying to figure out its special purpose for a long time."

From the ion channels expressed in hair cells and their associated calyces, the authors created the first computational model capable of quantitatively describing the nonquantal transmission of signals across this nanoscale gap. Simulating nonquantal transmission allowed the team to investigate what happens throughout the synaptic cleft, which is more extensive in vestibular synapses than other synapses.

"The mechanism turns out to be quite subtle, with dynamic interactions giving rise to fast and slow forms of nonquantal transmission," Raphael said. "To understand all this, we made a biophysical model of the synapse based on its detailed anatomy and physiology."

The model simulates the voltage response of the calyx to mechanical and electrical stimuli, tracking the flow of potassium ions through low-voltage-activated ion channels from pre-synaptic hair cells to the post-synaptic calyx.

Raphael said the model accurately predicted changes in potassium in the synaptic cleft, providing key new insights about changes in electrical potential that are responsible for the fast component of nonquantal transmission; explained how nonquantal transmission alone could trigger action potentials in the post-synaptic neuron; and showed how both fast and slow transmission depend on the close and extensive cup formed by the calyx on the hair cell.

Eatock said, "The key capability was the ability to predict the potassium level and electrical potential at every location within the cleft. This allowed the team to illustrate that the size and speed of nonquantal transmission depend on the novel structure of the calyx. The study demonstrates the power of engineering approaches to elucidate fundamental biological mechanisms, one of the important but sometimes overlooked goals of bioengineering research."

Quraishi began constructing the model and collaborating with Eatock in the mid-2000s when he was a graduate student in Raphael's research group and she was on the faculty of Baylor College of Medicine, just a few blocks from Rice in Houston's Texas Medical Center.

His first version of the model captured important features of the synapse, but he said gaps in "our knowledge of the specific potassium channels and other components that make up the model was too limited to claim it was entirely accurate."

Since then, Eatock, Lysakowski and others discovered ion channels in the calyx that transformed scientists' understanding of how ionic currents flow across hair cell and calyx membranes.

Qurashi said, "The unfinished work had weighed on me," and he was both relieved and excited when Govindaraju, a Ph.D. student in applied physics, joined Raphael's lab and resumed work on the model in 2018.

"By the time I started on the project, more data supported nonquantal transmission," Govindaraju said. "But the mechanism, especially that of fast transmission, was unclear. Building the model has given us a better understanding of the interplay and purpose of different ion channels, the calyx structure and dynamic changes in potassium and electric potential in the synaptic cleft."

Raphael said, "One of my very first grants was to develop a model of ion transport in the inner ear. It is always satisfying to achieve a unified mathematical model of a complex physiological process. For the past 30 years -- since the original observation of nonquantal transmission -- scientists have wondered, 'Why is this synapse so fast?' and, 'Is the transmission speed related to the unique calyx structure?' We have provided answers to both questions."

He said the link between the structure and function of the calyx "is an example of how evolution drives morphological specialization. A compelling argument can be made that once animals emerged from the sea and began to move on land, swing in trees and fly, there were increased demands on the vestibular system to rapidly inform the brain about the position of the head in space. And at this point the calyx appeared."

Raphael said the model opens the door for a deeper exploration of information processing in vestibular synapses, including research into the unique interactions between quantal and nonquantal transmission.

He said the model could also be a powerful tool for researchers who study electrical transmission in other parts of the nervous system, and he hopes it will aid those who design vestibular implants, neuroprosthetic devices that can restore function to those who have lost their balance.

Read more at Science Daily