Long-term transverse imaging of the hippocampus with glass microperiscopes.

The hippocampus consists of a stereotyped neuronal circuit repeated along the septal-temporal axis. This transverse circuit contains distinct subfields with stereotyped connectivity that support crucial cognitive processes, including episodic and spatial memory. However, comprehensive measurements across the transverse hippocampal circuit in vivo are intractable with existing techniques. Here, we developed an approach for two-photon imaging of the transverse hippocampal plane in awake mice via implanted glass microperiscopes, allowing optical access to the major hippocampal subfields and to the dendritic arbor of pyramidal neurons. Using this approach, we tracked dendritic morphological dynamics on CA1 apical dendrites and characterized spine turnover. We then used calcium imaging to quantify the prevalence of place and speed cells across subfields. Finally, we measured the anatomical distribution of spatial information, finding a non-uniform distribution of spatial selectivity along the DG-to-CA1 axis. This approach extends the existing toolbox for structural and functional measurements of hippocampal circuitry.

Stable representation of a naturalistic movie emerges from episodic activity with gain variability.

Visual cortical responses are known to be highly variable across trials within an experimental session. However, the long-term stability of visual cortical responses is poorly understood. Here using chronic imaging of V1 in mice we show that neural responses to repeated natural movie clips are unstable across weeks. Individual neuronal responses consist of sparse episodic activity which are stable in time but unstable in gain across weeks. Further, we find that the individual episode, instead of neuron, serves as the basic unit of the week-to-week fluctuation. To investigate how population activity encodes the stimulus, we extract a stable one-dimensional representation of the time in the natural movie, using an unsupervised method. Most week-to-week fluctuation is perpendicular to the stimulus encoding direction, thus leaving the stimulus representation largely unaffected. We propose that precise episodic activity with coordinated gain changes are keys to maintain a stable stimulus representation in V1.

Stimulus-dependent representational drift in primary visual cortex.

To produce consistent sensory perception, neurons must maintain stable representations of sensory input. However, neurons in many regions exhibit progressive drift across days. Longitudinal studies have found stable responses to artificial stimuli across sessions in visual areas, but it is unclear whether this stability extends to naturalistic stimuli. We performed chronic 2-photon imaging of mouse V1 populations to directly compare the representational stability of artificial versus naturalistic visual stimuli over weeks. Responses to gratings were highly stable across sessions. However, neural responses to naturalistic movies exhibited progressive representational drift across sessions. Differential drift was present across cortical layers, in inhibitory interneurons, and could not be explained by differential response strength or higher order stimulus statistics. However, representational drift was accompanied by similar differential changes in local population correlation structure. These results suggest representational stability in V1 is stimulus-dependent and may relate to differences in preexisting circuit architecture of co-tuned neurons.

Diverse coactive neurons encode stimulus-driven and stimulus-independent variables.

Both experimenter-controlled stimuli and stimulus-independent variables impact cortical neural activity. A major hurdle to understanding neural representation is distinguishing between qualitatively different causes of the fluctuating population activity. We applied an unsupervised low-rank tensor decomposition analysis to the recorded population activity in the visual cortex of awake mice in response to repeated presentations of naturalistic visual stimuli. We found that neurons covaried largely independently of individual neuron stimulus response reliability and thus encoded both stimulus-driven and stimulus-independent variables. Importantly, a neuron's response reliability and the neuronal coactivation patterns substantially reorganized for different external visual inputs. Analysis of recurrent balanced neural network models revealed that both the stimulus specificity and the mixed encoding of qualitatively different variables can arise from clustered external inputs. These results establish that coactive neurons with diverse response reliability mediate a mixed representation of stimulus-driven and stimulus-independent variables in the visual cortex.NEW & NOTEWORTHY V1 neurons covary largely independently of individual neuron's response reliability. A single neuron's response reliability imposes only a weak constraint on its encoding capabilities. Visual stimulus instructs a neuron's reliability and coactivation pattern. Network models revealed using clustered external inputs.

Management of acute and chronic vascular conditions of the hand.

Management of acute and chronic vascular disorders of the hand in patients with vasospastic and vaso-occlusive disorders is a complex problem and requires a multidisciplinary approach. The ischemia-related pain, skin ulcerations, and ultimately the threat of digital gangrene require a concerted effort to improve perfusion using a combination of medications and surgery. The purpose of this work is to review our experience over the past 2 decades with this cohort of patients including the variability of the clinical presentation, a method of classification, and a practical treatment philosophy.

Histological and radiographic comparison of allograft substitutes using a continuous delivery model in segmental defects.

Demineralized bone matrix (DBM) has been shown to possess osteoinductive capability and one of the specific bone morphogenetic proteins (BMPs) found within DBM that has been attributed with this osteoinductive ability is BMP-7, also known as osteogenic protein-1 (OP-1). The specific aims of this study were (1) to compare the treatment of segmental bone defects with OP-l and DBM in a rat femur model and (2) to determine the effects of the two treatments given at high and low doses via sustained release drug delivery. Animals in Group 1 acted as the control and Group 2 had a created segmental defect with plating and placement of a calcined tricalcium phosphate lysine (TCPL) capsule containing antibiotic (sham). Group 3 and 4 animals had a created segmental defect and received a TCPL carrier containing antibiotic along with DBM or OP-1, respectively. After 4 weeks post-implantation, animals were sacrificed before the retrieval of the bone. The femora were analyzed radiographically and histologically for bone growth. Analysis of the gross specimens showed considerable bone regeneration at low and high doses for both DBM and OP-1 when compared to the shams. At low levels bone regeneration between DBM and OP-1 was very similar. However, at high doses, OP-1 was shown to cause bone overgrowth with a greater curvature and an increased thickness of the distal and proximal ends of the femur. The stained slides showed the defects treated with DBM and OP-1 to be bridged with lamellar and woven bone that was continuous with the original bone. Histologically, the experimental femora demonstrated natural remodeling processes with new osteons and angiogenesis.