A fundamental impediment to understanding the brain is the availability of inexpensive and robust methods for targeting and manipulating specific neuronal populations. The need to overcome this barrier is pressing because there are considerable anatomical, physiological, cognitive, and behavioral differences between mice and higher mammalian species in which it is difficult to specifically target and manipulate genetically defined functional cell-types. In particular, it is unclear the degree to which insights from mouse models can shed light on the neural mechanisms that mediate cognitive functions in higher species including humans. Here we describe a novel recombinant adeno-associated virus (rAAV) that restricts gene expression to GABAergic interneurons within the telencephalon. We demonstrate that the viral expression is specific and robust, allowing for morphological visualization, activity monitoring and functional manipulation of interneurons in both mice and non-genetically tractable species, thus opening the possibility to study GABA-ergic function in virtually any vertebrate species.

Sensory deprivation can induce profound changes to central processing during developmental critical periods (CPs), and the recovery of normal function is maximal if the sensory input is restored during these epochs. Therefore, we asked whether mild and transient hearing loss (HL) during discrete CPs could induce changes to cortical cellular physiology. Electrical and inhibitory synaptic properties were obtained from auditory cortex pyramidal neurons using whole-cell recordings after bilateral earplug insertion or following earplug removal. Varying the age of HL onset revealed brief CPs of vulnerability for membrane and firing properties, as well as, inhibitory synaptic currents. These CPs closed 1 week after ear canal opening on postnatal day (P) 18. To examine whether the cellular properties could recover from HL, earplugs were removed prior to (P17) or after (P23), the closure of these CPs. The earlier age of hearing restoration led to greater recovery of cellular function, but firing rate remained disrupted. When earplugs were removed after the closure of these CPs, several changes persisted into adulthood. Therefore, long-lasting cellular deficits that emerge from transient deprivation during a CP may contribute to delayed acquisition of auditory skills in children who experience temporary HL.

SignificanceOur results indicate that nonhuman primates detect complex repeating acoustic sequences in a continuous auditory stream, which is an important precursor for human speech learning and perception. We demonstrate that oscillatory entrainment, known to support the attentive perception of rhythmic stimulus sequences, can occur for rhythms defined solely by stimulus context rather than physical boundaries. As opposed to acoustically driven entrainment by rhythmic tone sequences demonstrated previously, this form of entrainment relies on the brain’s ability to group auditory inputs based on their statistical regularities. The internally initiated, context-driven modulation of excitability in the medial pulvinar prior to A1 supports the notion of top-down entrainment.

The dorsal striatum has two functionally-defined subdivisions: a dorsomedial striatum (DMS) region involved in mediating goal-directed behaviors that require conscious effort, and a dorsolateral striatum (DLS) region involved in the execution of habitual behaviors in a familiar sensory context. Consistent with its presumed role in forming stimulus-response (S-R) associations, neurons in DLS receive massive inputs from sensorimotor cortex and are responsive to both active and passive sensory stimulation. While several studies have established that corticostriatal inputs contribute to the stimulus-induced responses observed in the DLS, there is growing awareness that the thalamus has a significant role in conveying sensory-related information to DLS and other parts of the striatum. The thalamostriatal projections to DLS originate mainly from the caudal intralaminar region, which contains the parafascicular (Pf) nucleus, and from higher-order thalamic nuclei such as the medial part of the posterior (POm) nucleus. Based on recent findings, we hypothesize that the thalamostriatal projections from these two regions exert opposing influences on the expression of behavioral habits. This article reviews the subcortical circuits that regulate the transmission of sensory information through these thalamostriatal projection systems, and describes the evidence that indicates these circuits could be manipulated to ameliorate the symptoms of Parkinson’s disease (PD) and related neurological disorders.

The primate somatosensory system provides an excellent model system with which to investigate adult neural plasticity. We have previously shown that transection of the median and ulnar nerves is followed by an expansion in the representation of radial nerve skin, and that this plasticity proceeds in stages. Immediately following nerve injury, new receptive fields are "unmasked" in a fraction of the affected cortex. The remaining deprived cortex regains responsiveness to tactile stimulation over the following days to weeks. Given these progressive changes, it has been suggested that different mechanisms might account for the earlier and later phases of reorganization. In the present experiments, we have quantified receptor autoradiographic binding data for GABA A and GABA B , AMPA, and NMDA receptors in the primary somatosensory cortices of adult squirrel monkeys at four post-nerve injury survival durations: immediately (1-3 hr), 3-days, 1-month, and 2-months. We find dramatic reductions in GABA A binding in layer IV within hours following nerve injury, and this reduction is maintained across all survival durations. This finding is consistent with the idea that the earliest reorganizational changes are due to a relaxation in tonic inhibitory mechanisms permitting the expression of formerly subthreshold receptive fields. GABA B receptor binding is decreased in layer IV by 1 month after nerve injury, while binding for AMPA receptors is increased in layer IV by this time. These findings are consistent with our previous suggestion that the second stage of reorganization proceeds via mechanisms comparable to those revealed to account for NMDA-dependent long-term potentiation in the hippocampus.