Rhythmic whisking area (RW) in rat primary motor cortex: an internal monitor of movement-related signals?

Vibrissae-related sensorimotor cortex controls whisking movements indirectly via modulation of lower-level sensorimotor loops and a brainstem central pattern generator (CPG). Two different whisker representations in primary motor cortex (vM1) affect whisker movements in different ways. Prolonged microstimulation in RF, a larger anterior subregion of vM1, gives rise to complex face movements and whisker retraction while the same stimulation evokes large-amplitude rhythmic whisker movement in a small caudo-medial area (RW). To characterize the motor cortex representation of explorative whisking movements, here we recorded RW units in head-fixed rats trained to contact a moving object with one whisker. RW single units were found to encode two aspects of whisker movement independently, albeit on slow time scales (hundreds of milliseconds). The first is whisker position. The second consists of speed (absolute velocity), intensity (instantaneous power), and frequency (spectral centroid). The coding for the latter three parameters was tightly correlated and realized by a continuum of RW responses-ranging from a preference of movement to a preference of rest. Information theory analysis indicated that RW spikes carry most information about position and frequency, while intensity and speed are less well represented. Further, investigating multiple and single RW units, we found a lack of phase locking, movement anticipation, and contact-related tactile responses. These findings suggest that RW neither programs detailed whisker trajectories nor initiates them. Nor does it play a role in processing object touch. Its relationship to whisking is thus indirect and may be related to movement monitoring, perhaps using feedback from the CPG.

Intrinsic connections in the anterior part of the bed nucleus of the stria terminalis.

Intrinsic connections in the anterior portion of the bed nucleus of the stria terminalis (BNST-A) were studied using patch recordings and ultraviolet (UV) glutamate uncaging (GU) in vitro. UV light was delivered at small BNST-A sites in a grid-like pattern while evoked responses were monitored in different BNST-A regions. Three sectors were distinguished in the BNST-A using fiber bundles readily identifiable in transilluminated slices: the anterior commissure, dividing the BNST-A into dorsal and ventral (BNST-AV) regions, and the intra-BNST component of the stria terminalis, subdividing the dorsal portion into medial (BNST-AM) and lateral (BNST-AL) regions. Overall, GU elicited GABAergic inhibitory postsynaptic potentials (IPSPs) more frequently than excitatory postsynaptic potentials. The incidence of intraregional connections was higher than interregional links. With respect to the latter, asymmetric connections were seen between different parts of the BNST-A. Indeed, while reciprocal connections were found between the BNST-AL and BNST-AM, BNST-AL to BNST-AM connections were more frequent than in the opposite direction. Similarly, while GU in the BNST-AM or BNST-AL often elicited IPSPs in BNST-AV cells, the opposite was rarely seen. Within the BNST-AM, connections were polarized, with dorsal GU sites eliciting IPSPs in more ventrally located cells more frequently than the opposite. This trend was not seen in other regions of the BNST. Consistent with this, most BNST-AM cells had dorsally directed dendrites and ventrally ramified axons, whereas this morphological polarization was not seen in other parts of the BNST-A. Overall, our results reveal a hitherto unsuspected level of asymmetry in the connections within and between different BNST-A regions, implying a degree of interdependence in their activity.

Contrasting distribution of physiological cell types in different regions of the bed nucleus of the stria terminalis.

We characterized the electroresponsive and morphological properties of neurons in the bed nucleus of the stria terminalis (BNST). Previously, Rainnie and colleagues distinguished three cell types in the anterolateral region of BNST (BNST-AL): low-threshold bursting cells (LTB; type II) and regular spiking neurons that display time-dependent (RS; type I) or fast (fIR; type III) inward rectification in the hyperpolarizing direction (Hammack SE, Mania I, Rainnie DG. J Neurophysiol 98: 638-56, 2007). We report that the same neuronal types exist in the anteromedial (AM) and anteroventral (AV) regions of BNST. In addition, we observed two hitherto unreported cell types: late-firing (LF) cells, only seen in BNST-AL, that display a conspicuous delay to firing, and spontaneously active (SA) neurons, only present in BNST-AV, firing continuously at rest. However, the feature that most clearly distinguished the three BNST regions was the incidence of LTB cells (approximately 40-70%) and the strength of their bursting behavior (both higher in BNST-AM and AV relative to AL). The incidence of RS cells was similar in the three regions (∼25%), whereas that of fIR cells was higher in BNST-AL (∼25%) than AV or AM (≤8%). With the use of biocytin, two dominant morphological cell classes were identified but they were not consistently related to particular physiological phenotypes. One neuronal class had highly branched and spiny dendrites; the second had longer but poorly branched and sparsely spiny dendrites. Both often exhibited dendritic varicosities. Since LTB cells prevail in BNST, it will be important to determine what inputs set their firing mode (tonic vs. bursting) and in what behavioral states.

Impact of predatory threat on fear extinction in Lewis rats.

Humans with post-traumatic stress disorder (PTSD) are deficient at extinguishing conditioned fear responses. A study of identical twins concluded that this extinction deficit does not predate trauma but develops as a result of trauma. The present study tested whether the Lewis rat model of PTSD reproduces these features of the human syndrome. Lewis rats were subjected to classical auditory fear conditioning before or after exposure to a predatory threat that mimics a type of traumatic stress that leads to PTSD in humans. Exploratory behavior on the elevated plus maze 1 wk after predatory threat exposure was used to distinguish resilient vs. PTSD-like rats. Properties of extinction varied depending on whether fear conditioning and extinction occurred before or after predatory threat. When fear conditioning was carried out after predatory threat, PTSD-like rats showed a marked extinction deficit compared with resilient rats. In contrast, no differences were seen between resilient and PTSD-like rats when fear conditioning and extinction occurred prior to predatory threat. These findings in Lewis rats closely match the results seen in humans with PTSD, thereby suggesting that studies comparing neuronal interactions in resilient vs. at-risk Lewis rats might shed light on the causes and pathophysiology of human PTSD.