Direct Approach or Detour: A Comparative Model of Inhibition and Neural Ensemble Size in Behavior Selection

Organisms must cope with different risk/reward landscapes in their ecological niche. Hence, species have evolved behavior and cognitive processes to optimally balance approach and avoidance. Navigation through space, including taking detours, appears also to be an essential element of consciousness. Such processes allow organisms to negotiate predation risk and natural geometry that obstruct foraging. One aspect of this is the ability to inhibit a direct approach toward a reward. Using an adaptation of the well-known detour paradigm in comparative psychology, but in a virtual world, we simulate how different neural configurations of inhibitive processes can yield behavior that approximates characteristics of different species. Results from simulations may help elucidate how evolutionary adaptation can shape inhibitive processing in particular and behavioral selection in general. More specifically, results indicate that both the level of inhibition that an organism can exert and the size of neural populations dedicated to inhibition contribute to successful detour navigation. According to our results, both factors help to facilitate detour behavior, but the latter (i.e., larger neural populations) appears to specifically reduce behavioral variation.

A Brainstem reticulotegmental neural ensemble drives acoustic startle reflexes

The reticulotegmental nucleus (RtTg) has long been recognized as a crucial component of brainstem reticular formation (RF). However, the function of RtTg and its related circuits remain elusive. Here, we report a role of the RtTg in startle reflex, a highly conserved innate defensive behaviour. Optogenetic activation of RtTg neurons evokes robust startle responses in mice. The glutamatergic neurons in the RtTg are significantly activated during acoustic startle reflexes (ASR). Chemogenetic inhibition of the RtTg glutamatergic neurons decreases the ASR amplitudes. Viral tracing reveals an ASR neural circuit that the cochlear nucleus carrying auditory information sends direct excitatory innervations to the RtTg glutamatergic neurons, which in turn project to spinal motor neurons. Together, our findings describe a functional role of RtTg and its related neural circuit in startle reflexes, and demonstrate how the RF connects auditory system with motor functions.

Synchrony-Division Neural Multiplexing: An Encoding Model

Cortical neurons receive mixed information from collective spiking activities of primary sensory neurons in response to a sensory stimulus. A recent study demonstrated that the time underlying the onset-offset of a tactile stimulus and its varying intensity can be respectively represented by synchronous and asynchronous spikes of S1 neurons in rats. This evidence capitalized on the ability of an ensemble of homogeneous neurons to multiplex, a coding strategy that was referred to as synchrony division multiplexing (SDM). Although neural multiplexing can be conceived by distinct functions of individual neurons in a heterogeneous neural ensemble, the extent to which nearly identical neurons in a homogeneous neural ensemble encode multiple features of a mixed stimulus remains unknown. Here, we present a computational framework to provide a system-level understanding of how an ensemble of homogeneous neurons enables SDM. First, we simulate SDM with an ensemble of homogeneous conductance-based model neurons receiving a mixed stimulus comprising slow and fast features. Using feature estimation techniques, we show that both features of the stimulus can be inferred from the generated spikes. Second, we utilize linear nonlinear (LNL) cascade models and calculate temporal filters and static nonlinearities of differentially synchronized spikes. We demonstrate that these filters and nonlinearities are distinct for synchronous and asynchronous spikes. Finally, we develop an augmented LNL cascade model as an encoding model for the SDM by combining individual LNLs calculated for each type of spike. The augmented LNL model reveals that a homogeneous neural ensemble can perform two different functions, namely, temporal- and rate- coding, simultaneously.

The orbitofrontal cortex maps future navigational goals

Accurate navigation to a desired goal requires consecutive estimates of spatial relationships between the current position and future destination throughout the journey. Although neurons in the hippocampal formation can represent the position of an animal as well as its nearby trajectories1–7, their role in determining the destination of the animal has been questioned8,9. It is, thus, unclear whether the brain can possess a precise estimate of target location during active environmental exploration. Here we describe neurons in the rat orbitofrontal cortex (OFC) that form spatial representations persistently pointing to the subsequent goal destination of an animal throughout navigation. This destination coding emerges before the onset of navigation, without direct sensory access to a distal goal, and even predicts the incorrect destination of an animal at the beginning of an error trial. Goal representations in the OFC are maintained by destination-specific neural ensemble dynamics, and their brief perturbation at the onset of a journey led to a navigational error. These findings suggest that the OFC is part of the internal goal map of the brain, enabling animals to navigate precisely to a chosen destination that is beyond the range of sensory perception.

Multifunctional Cre-dependent transgenic mice for high-precision all-optical interrogation of neural circuits

Causally relating the detailed structure and function of neural circuits to behavior requires the ability to precisely and simultaneously write-in and read-out neural activity. All optical systems that combine two photon (2p) calcium imaging and targeted photostimulation provide such an approach, but require co-expression of an activity indicator, such as GCaMP, and an optogenetic actuator, ideally a potent soma-targeted opsin. In the mammalian brain, such co-expression has so far been achieved by viral transduction, which is invasive and can produce variable, focal, and sometimes toxic overexpression. To overcome this challenge, we developed and validated a Cre-reporter mouse ("Ai203") that conditionally expresses a soma-targeted opsin, ChroME, fused to GCaMP7s. 1p or 2p illumination of expressing neurons in vitro and in vivo produces powerful, precise activation comparable to viral expression of ChroME. The soma-targeted GCaMP7s provides sensitive activity measurements for tracking physiological activity, and the soma-targeted ChroME provides powerful control over neural ensemble activity with holographic optogenetics. We further demonstrate the use of the Ai203 reporter line in 1p optogenetic manipulation of performance on a cortex-dependent visual task and in 2p synaptic connectivity mapping. This new transgenic line could thus greatly facilitate the study of neural circuits by providing a flexible, convenient, and stable tool for all-optical access to large, cell-type specific neural populations throughout the nervous system.