Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys.

Optogenetic tools have opened a rich experimental landscape for understanding neural function and disease. Here, we present the first validation of eight optogenetic constructs driven by recombinant adeno-associated virus (AAV) vectors and a WGA-Cre based dual injection strategy for projection targeting in a widely-used New World primate model, the common squirrel monkey Saimiri sciureus. We observed opsin expression around the local injection site and in axonal projections to downstream regions, as well as transduction to thalamic neurons, resembling expression patterns observed in macaques. Optical stimulation drove strong, reliable excitatory responses in local neural populations for two depolarizing opsins in anesthetized monkeys. Finally, we observed continued, healthy opsin expression for at least one year. These data suggest that optogenetic tools can be readily applied in squirrel monkeys, an important first step in enabling precise, targeted manipulation of neural circuits in these highly trainable, cognitively sophisticated animals. In conjunction with similar approaches in macaques and marmosets, optogenetic manipulation of neural circuits in squirrel monkeys will provide functional, comparative insights into neural circuits which subserve dextrous motor control as well as other adaptive behaviors across the primate lineage. Additionally, development of these tools in squirrel monkeys, a well-established model system for several human neurological diseases, can aid in identifying novel treatment strategies.

Continuous infusion of propofol or intermittent bolus of tiletamine-zolazepam in squirrel monkeys (Saimiri sciureus).

OBJECTIVE: To investigate an infusion of propofol for anesthesia in comparison to tiletamine-zolazepam anesthesia, evaluating physiological variables and recovery in squirrel monkeys. STUDY DESIGN: Prospective non-blinded randomized study. ANIMALS: Eight healthy squirrel monkeys (Saimiri sciureus), aged 3 years and weighing 0.340-0.695 kg. METHODS: Premedication was intramuscular midazolam (0.5 mg) and meperidine (4 mg). Anesthesia was induced with intravenous (IV) propofol (4 mg kg(-1)  minute(-1) ) and maintained with propofol starting at 0.4 mg kg(-1)  minute(-1) (PRO, n = 4) or IV tiletamine-zolazepam (5 mg kg(-1) ) and maintained with supplementary doses of TZ (TZ, n = 4). Cardiopulmonary variables were measured continuously. Arterial blood gases and lactate concentration were measured at the end of anesthesia. Quality and times of recovery were determined. Repeatedly measured data for significant differences were tested between groups with t-test and within groups by anova. RESULTS: Median time for induction of anesthesia in PRO was 180 seconds. Mean maintenance infusion rate of propofol was 0.43 ± 0.05 mg kg(-1)  minute(-1) , varying during the 1 hour period. One monkey died after administration of TZ; others required 1, 4, or 8 supplemental doses. Cardiopulmonary variables were similar between groups, but hypotension was recorded. Recovery times to ventral recumbency in PRO (32 ± 17 minutes) and TZ (84 ± 11 minutes) and normal ambulation in PRO (58 ± 22 minutes) and TZ (358 ± 109minutes) were significantly different (p < 0.05). Recovery quality was superior in PRO, with less ataxia and fewer unsuccessful attempts to stand. Lactate concentration was not different between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Cardiopulmonary variables were similar between protocols, aside from the higher incidence of hypotension in PRO, indicating that further studies with a larger number of animals are required. Compared to tiletamine-zolazepam, propofol anesthesia provided faster and superior anesthetic recovery in these animals.

Anatomy and morphometric aspects of the trachea of Saimiri sciureus Linnaeus, 1758: knowledge for emergency procedures.

The aim of this work is to study the morphological characteristics of the trachea of Saimiri sciureus through quantification and measurement of the cartilaginous rings, providing information to facilitate the election of more appropriate endotracheal tube, laryngeal mask or tracheostomy tube for anesthetic and emergency procedures, as it is a species of Neotropical primates most commonly used as biological models, and little is known about their morphology. Nine animals were investigated, being 4 adults and 5 young acquired from the Centro Nacional de Primatas (National Primate Center - CENP) - Ananindeua - PA, which died from natural causes and then fixed in aqueous buffered formalin 10%. Saimiri sciureus trachea comprises an average of 32.8 incomplete rings and an average length of 3.74 cm in young animals, while in adults it demonstrated an average of 30.25 rings and average length of 3.67 cm. The shape of the light and its proportion varied along the trachea. Endotracheal tube with a diameter the 2.0 - 2.5 mm, laryngeal mask number 1.0 or tracheostomy tube neonatal Shiley number 3.0, can be placed in animals weighing 600 g - 1.2 Kg. Given the great importance of the species studied, which is widely used as a biological model, the detailing on the morphology and morphometry of tracheal animal studies provides new approaches needed in respiratory emergency, as well as, facilitates the development of future anesthetic protocols.

Traumatic elbow luxation repair in a common squirrel monkey (Saimiri Sciureus) and a bonnet macaque (Macaca radiata).

Traumatic elbow luxation was diagnosed in a common squirrel monkey (Saimiri sciureus) and a bonnet macaque (Macaca radiata). In the common squirrel monkey, the luxation was complicated by an ulnar fracture and would not stay reduced when attempts at closed reduction were made. The luxation was surgically reduced and a transarticular type I external skeletal fixator was placed. In the bonnet macaque, closed reduction was performed and the elbow was stabilized using a cast. Both monkeys regained good function of the injured elbows.

A squirrel monkey model of poststroke motor recovery.

Nonhuman primate models of poststroke recovery have become increasingly rare primarily due to high purchase and maintenance costs and limited availability of nonhuman primate species. Despite this obstacle, nonhuman primate models may offer important advantages over rodent models for understanding many of the brain's mechanisms for self-repair due to greater similarity in cortical organization to humans. Since the mid-1990s, surgical, neurophysiological, and neuroanatomical methods have been developed to understand structural and functional remodeling of the cerebral cortex after an ischemic event, such as occurs in stroke. These methods require long surgical procedures and entail constant physiological monitoring. With careful attention to intraoperative and postsurgical monitoring, these procedures can be repeated multiple times in individual monkeys without untoward events. This model provides a statistically powerful approach for tracking brain plasticity in the ensuing weeks and months after a stroke-like injury, reducing the number of animals required for individual experiments. This methodology is described in detail, and many of the resulting findings that are relevant for understanding stroke recovery and the effects of rehabilitative and pharmacotherapeutic interventions are summarized.