Finding the beat: a neural perspective across humans and non-human primates

Humans possess an ability to perceive and synchronize movements to the beat in music (‘beat perception and synchronization’), and recent neuroscientific data have offered new insights into this beat-finding capacity at multiple neural levels. Here, we review and compare behavioural and neural data on temporal and sequential processing during beat perception and entrainment tasks in macaques (including direct neural recording and local field potential (LFP)) and humans (including fMRI, EEG and MEG). These abilities rest upon a distributed set of circuits that include the motor cortico-basal-ganglia–thalamo-cortical (mCBGT) circuit, where the supplementary motor cortex (SMA) and the putamen are critical cortical and subcortical nodes, respectively. In addition, a cortical loop between motor and auditory areas, connected through delta and beta oscillatory activity, is deeply involved in these behaviours, with motor regions providing the predictive timing needed for the perception of, and entrainment to, musical rhythms. The neural discharge rate and the LFP oscillatory activity in the gamma- and beta-bands in the putamen and SMA of monkeys are tuned to the duration of intervals produced during a beat synchronization–continuation task (SCT). Hence, the tempo during beat synchronization is represented by different interval-tuned cells that are activated depending on the produced interval. In addition, cells in these areas are tuned to the serial-order elements of the SCT. Thus, the underpinnings of beat synchronization are intrinsically linked to the dynamics of cell populations tuned for duration and serial order throughout the mCBGT. We suggest that a cross-species comparison of behaviours and the neural circuits supporting them sets the stage for a new generation of neurally grounded computational models for beat perception and synchronization.     

Multiple gamma rhythms carry distinct spatial frequency information in primary visual cortex

Gamma rhythms in many brain regions, including the primary visual cortex (V1), are thought to play a role in information processing. Here, we report a surprising finding of 3 narrowband gamma rhythms in V1 that processed distinct spatial frequency (SF) signals and had different neural origins. The low gamma (LG; 25 to 40 Hz) rhythm was generated at the V1 superficial layer and preferred a higher SF compared with spike activity, whereas both the medium gamma (MG; 40 to 65 Hz), generated at the cortical level, and the high gamma HG; (65 to 85 Hz), originated precortically, preferred lower SF information. Furthermore, compared with the rates of spike activity, the powers of the 3 gammas had better performance in discriminating the edge and surface of simple objects. These findings suggest that gamma rhythms reflect the neural dynamics of neural circuitries that process different SF information in the visual system, which may be crucial for multiplexing SF information and synchronizing different features of an object.

Gamma rhythms in many brain regions are thought to play a role in information processing. This study reports the surprising coexistence of three narrow-band gamma rhythms in visual cortex with distinct coding properties for visual features and distinct neural origins.     

Neural circuit models for computations in early visual cortex

Some cortical circuit models study the mechanisms of the transforms from visual inputs to neural responses. They model neural properties such as feature tunings, pattern sensitivities, and how they depend on intracortical connections and contextual inputs. Other cortical circuit models are more concerned with computational goals of the transform from visual inputs to neural responses, or the roles of the neural responses in the visual behavior. The appropriate complexity of a cortical circuit model depends on the question asked. Modeling neural circuits of many interacting hypercolumns is a necessary challenge, which is providing insights to cortical computations, such as visual saliency computation, and linking physiology with global visual cognitive behavior such as bottom-up attentional selection.     

Development of Circadian Oscillators in Neurosphere Cultures during Adult Neurogenesis

Circadian rhythms are common in many cell types but are reported to be lacking in embryonic stem cells. Recent studies have described possible interactions between the molecular mechanism of circadian clocks and the signaling pathways that regulate stem cell differentiation. Circadian rhythms have not been examined well in neural stem cells and progenitor cells that produce new neurons and glial cells during adult neurogenesis. To evaluate circadian timing abilities of cells undergoing neural differentiation, neurospheres were prepared from the mouse subventricular zone (SVZ), a rich source of adult neural stem cells. Circadian rhythms in mPer1 gene expression were recorded in individual spheres, and cell types were characterized by confocal immunofluorescence microscopy at early and late developmental stages in vitro. Circadian rhythms were observed in neurospheres induced to differentiate into neurons or glia, and rhythms emerged within 3–4 days as differentiation proceeded, suggesting that the neural stem cell state suppresses the functioning of the circadian clock. Evidence was also provided that neural stem progenitor cells derived from the SVZ of adult mice are self-sufficient clock cells capable of producing a circadian rhythm without input from known circadian pacemakers of the organism. Expression of mPer1 occurred in high frequency oscillations before circadian rhythms were detected, which may represent a role for this circadian clock gene in the fast cycling of gene expression responsible for early cell differentiation.     

Learning to link visual contours

In complex visual scenes, linking related contour elements is important for object recognition. This process, thought to be stimulus driven and hard wired, has substrates in primary visual cortex (V1). Here, however, we find contour integration in V1 to depend strongly on perceptual learning and top-down influences that are specific to contour detection. In naive monkeys, the information about contours embedded in complex backgrounds is absent in V1 neuronal responses and is independent of the locus of spatial attention. Training animals to find embedded contours induces strong contour-related responses specific to the trained retinotopic region. These responses are most robust when animals perform the contour detection task but disappear under anesthesia. Our findings suggest that top-down influences dynamically adapt neural circuits according to specific perceptual tasks. This may serve as a general neuronal mechanism of perceptual learning and reflect top-down mediated changes in cortical states.     

Noisy Galvanic Vestibular Stimulation Modulates the Amplitude of EEG Synchrony Patterns

Noisy galvanic vestibular stimulation has been associated with numerous cognitive and behavioural effects, such as enhancement of visual memory in healthy individuals, improvement of visual deficits in stroke patients, as well as possibly improvement of motor function in Parkinson’s disease; yet, the mechanism of action is unclear. Since Parkinson’s and other neuropsychiatric diseases are characterized by maladaptive dynamics of brain rhythms, we investigated whether noisy galvanic vestibular stimulation was associated with measurable changes in EEG oscillatory rhythms within theta (4–7.5 Hz), low alpha (8–10 Hz), high alpha (10.5–12 Hz), beta (13–30 Hz) and gamma (31–50 Hz) bands. We recorded the EEG while simultaneously delivering noisy bilateral, bipolar stimulation at varying intensities of imperceptible currents – at 10, 26, 42, 58, 74 and 90% of sensory threshold – to ten neurologically healthy subjects. Using standard spectral analysis, we investigated the transient aftereffects of noisy stimulation on rhythms. Subsequently, using robust artifact rejection techniques and the Least Absolute Shrinkage Selection Operator regression and cross-validation, we assessed the combinations of channels and power spectral features within each EEG frequency band that were linearly related with stimulus intensity. We show that noisy galvanic vestibular stimulation predominantly leads to a mild suppression of gamma power in lateral regions immediately after stimulation, followed by delayed increase in beta and gamma power in frontal regions approximately 20–25 s after stimulation ceased. Ongoing changes in the power of each oscillatory band throughout frontal, central/parietal, occipital and bilateral electrodes predicted the intensity of galvanic vestibular stimulation in a stimulus-dependent manner, demonstrating linear effects of stimulation on brain rhythms. We propose that modulation of neural oscillations is a potential mechanism for the previously-described cognitive and motor effects of vestibular stimulation, and noisy galvanic vestibular stimulation may provide an additional non-invasive means for neuromodulation of functional brain networks.     

Alpha-Band Rhythms in Visual Task Performance: Phase-Locking by Rhythmic Sensory Stimulation

Oscillations are an important aspect of neuronal activity. Interestingly, oscillatory patterns are also observed in behaviour, such as in visual performance measures after the presentation of a brief sensory event in the visual or another modality. These oscillations in visual performance cycle at the typical frequencies of brain rhythms, suggesting that perception may be closely linked to brain oscillations. We here investigated this link for a prominent rhythm of the visual system (the alpha-rhythm, 8–12 Hz) by applying rhythmic visual stimulation at alpha-frequency (10.6 Hz), known to lead to a resonance response in visual areas, and testing its effects on subsequent visual target discrimination. Our data show that rhythmic visual stimulation at 10.6 Hz: 1) has specific behavioral consequences, relative to stimulation at control frequencies (3.9 Hz, 7.1 Hz, 14.2 Hz), and 2) leads to alpha-band oscillations in visual performance measures, that 3) correlate in precise frequency across individuals with resting alpha-rhythms recorded over parieto-occipital areas. The most parsimonious explanation for these three findings is entrainment (phase-locking) of ongoing perceptually relevant alpha-band brain oscillations by rhythmic sensory events. These findings are in line with occipital alpha-oscillations underlying periodicity in visual performance, and suggest that rhythmic stimulation at frequencies of intrinsic brain-rhythms can be used to reveal influences of these rhythms on task performance to study their functional roles.     

Hippocampal theta oscillations are slower in humans than in rodents: implications for models of spatial navigation and memory

The theta oscillation is a neuroscience enigma. When a rat runs through an environment, large-amplitude theta oscillations (4–10 Hz) reliably appear in the hippocampus''s electrical activity. The consistency of this pattern led to theta playing a central role in theories on the neural basis of mammalian spatial navigation and memory. However, in fact, hippocampal oscillations at 4–10 Hz are rare in humans and in some other species. This presents a challenge for theories proposing theta as an essential component of the mammalian brain, including models of place and grid cells. Here, I examine this issue by reviewing recent research on human hippocampal oscillations using direct brain recordings from neurosurgical patients. This work indicates that the human hippocampus does indeed exhibit rhythms that are functionally similar to theta oscillations found in rodents, but that these signals have a slower frequency of approximately 1–4 Hz. I argue that oscillatory models of navigation and memory derived from rodent data are relevant for humans, but that they should be modified to account for the slower frequency of the human theta rhythm.     

Alterations in brain connectivity underlying beta oscillations in Parkinsonism

Cortico-basal ganglia-thalamocortical circuits are severely disrupted by the dopamine depletion of Parkinson's disease (PD), leading to pathologically exaggerated beta oscillations. Abnormal rhythms, found in several circuit nodes are correlated with movement impairments but their neural basis remains unclear. Here, we used dynamic causal modelling (DCM) and the 6-hydroxydopamine-lesioned rat model of PD to examine the effective connectivity underlying these spectral abnormalities. We acquired auto-spectral and cross-spectral measures of beta oscillations (10-35 Hz) from local field potential recordings made simultaneously in the frontal cortex, striatum, external globus pallidus (GPe) and subthalamic nucleus (STN), and used these data to optimise neurobiologically plausible models. Chronic dopamine depletion reorganised the cortico-basal ganglia-thalamocortical circuit, with increased effective connectivity in the pathway from cortex to STN and decreased connectivity from STN to GPe. Moreover, a contribution analysis of the Parkinsonian circuit distinguished between pathogenic and compensatory processes and revealed how effective connectivity along the indirect pathway acquired a strategic importance that underpins beta oscillations. In modelling excessive beta synchrony in PD, these findings provide a novel perspective on how altered connectivity in basal ganglia-thalamocortical circuits reflects a balance between pathogenesis and compensation, and predicts potential new therapeutic targets to overcome dysfunctional oscillations.     

Respiration modulates oscillatory neural network activity at rest

Despite recent advances in understanding how respiration affects neural signalling to influence perception, cognition, and behaviour, it is yet unclear to what extent breathing modulates brain oscillations at rest. We acquired respiration and resting state magnetoencephalography (MEG) data from human participants to investigate if, where, and how respiration cyclically modulates oscillatory amplitudes (2 to 150 Hz). Using measures of phase–amplitude coupling, we show respiration-modulated brain oscillations (RMBOs) across all major frequency bands. Sources of these modulations spanned a widespread network of cortical and subcortical brain areas with distinct spectrotemporal modulation profiles. Globally, delta and gamma band modulations varied with distance to the head centre, with stronger modulations at distal (versus central) cortical sites. Overall, we provide the first comprehensive mapping of RMBOs across the entire brain, highlighting respiration–brain coupling as a fundamental mechanism to shape neural processing within canonical resting state and respiratory control networks (RCNs).

Despite recent advances, it remains unclear to what extent breathing modulates brain oscillations at rest. This magnetoencephalography study in human participants identifies a widespread brain network of neural oscillations that are coupled to the respiratory rhythm.     

Impairment of Cognitive Function and Synaptic Plasticity Associated with Alteration of Information Flow in Theta and Gamma Oscillations in Melamine-Treated Rats

Changes of neural oscillations at a variety of physiological rhythms are effectively associated with cognitive performance. The present study investigated whether the directional indices of neural information flow (NIF) could be used to symbolize the synaptic plasticity impairment in hippocampal CA3-CA1 network in a rat model of melamine. Male Wistar rats were employed while melamine was administered at a dose of 300 mg/kg/day for 4 weeks. Behavior was measured by the Morris water maze(MWM)test. Local field potentials (LFPs) were recorded before long-term potentiation (LTP) induction. Generalized partial directed coherence (gPDC) and phase-amplitude coupling conditional mutual information (PAC_CMI) were used to measure the unidirectional indices in both theta and low gamma oscillations (LG, ∼30–50 Hz). Our results showed that melamine induced the cognition deficits consistent with the reduced LTP in CA1 area. Phase locking values (PLVs) showed that the synchronization between CA3 and CA1 in both theta and LG rhythms was reduced by melamine. In both theta and LG rhythms, unidirectional indices were significantly decreased in melamine treated rats while a similar variation trend was observed in LTP reduction, implying that the effects of melamine on cognitive impairment were possibly mediated via profound alterations of NIF on CA3-CA1 pathway in hippocampus. The results suggested that LFPs activities at these rhythms were most likely involved in determining the alterations of information flow in the hippocampal CA3-CA1 network, which might be associated with the alteration of synaptic transmission to some extent.     

Abnormal Astrocytosis in the Basal Ganglia Pathway of Git1?/? Mice

Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, affecting approximately 5% of children. However, the neural mechanisms underlying its development and treatment are yet to be elucidated. In this study, we report that an ADHD mouse model, which harbors a deletion in the Git1 locus, exhibits severe astrocytosis in the globus pallidus (GP) and thalamic reticular nucleus (TRN), which send modulatory GABAergic inputs to the thalamus. A moderate level of astrocytosis was displayed in other regions of the basal ganglia pathway, including the ventrobasal thalamus and cortex, but not in other brain regions, such as the caudate putamen, basolateral amygdala, and hippocampal CA1. This basal ganglia circuit-selective astrocytosis was detected in both in adult (2–3 months old) and juvenile (4 weeks old) Git1^−/− mice, suggesting a developmental origin. Astrocytes play an active role in the developing synaptic circuit; therefore, we performed an immunohistochemical analysis of synaptic markers. We detected increased and decreased levels of GABA and parvalbumin (PV), respectively, in the GP. This suggests that astrocytosis may alter synaptic transmission in the basal ganglia. Intriguingly, increased GABA expression colocalized with the astrocyte marker, GFAP, indicative of an astrocytic origin. Collectively, these results suggest that defects in basal ganglia circuitry, leading to impaired inhibitory modulation of the thalamus, are neural correlates for the ADHD-associated behavioral manifestations in Git1^−/− mice.     

Collinear Stimuli Induce Local and Cross-Areal Coherence in the Visual Cortex of Behaving Monkeys

Background

Collinear patterns of local visual stimuli are used to study contextual effects in the visual system. Previous studies have shown that proximal collinear flankers, unlike orthogonal, can enhance the detection of a low contrast central element. However, the direct neural interactions between cortical populations processing the individual flanker elements and the central element are largely unknown.

Methodology/Principal Findings

Using voltage-sensitive dye imaging (VSDI) we imaged neural population responses in V1 and V2 areas in fixating monkeys while they were presented with collinear or orthogonal arrays of Gabor patches. We then studied the spatio-temporal interactions between neuronal populations processing individual Gabor patches in the two conditions. Time-frequency analysis of the stimulus-evoked VSDI signal showed power increase mainly in low frequencies, i.e., the alpha band (α; 7–14 Hz). Power in the α-band was more discriminative at a single trial level than other neuronal population measures. Importantly, the collinear condition showed an increased intra-areal (V1-V1 and V2-V2) and inter-areal (V1-V2) α-coherence with shorter latencies than the orthogonal condition, both before and after the removal of the stimulus contribution. α-coherence appeared between discrete neural populations processing the individual Gabor patches: the central element and the flankers.

Conclusions/Significance

Our findings suggest that collinear effects are mediated by synchronization in a distributed network of proximal and distant neuronal populations within and across V1 and V2.     

Separating Fusion from Rivalry

Visual fusion is the process in which differing but compatible binocular information is transformed into a unified percept. Even though this is at the basis of binocular vision, the underlying neural processes are, as yet, poorly understood. In our study we therefore aimed to investigate neural correlates of visual fusion. To this end, we presented binocularly compatible, fusible (BF), and incompatible, rivaling (BR) stimuli, as well as an intermediate stimulus type containing both binocularly fusible and monocular, incompatible elements (BFR). Comparing BFR stimuli with BF and BR stimuli, respectively, we were able to disentangle brain responses associated with either visual fusion or rivalry. By means of functional magnetic resonance imaging, we measured brain responses to these stimulus classes in the visual cortex, and investigated them in detail at various retinal eccentricities. Compared with BF stimuli, the response to BFR stimuli was elevated in visual cortical areas V1 and V2, but not in V3 and V4 – implying that the response to monocular stimulus features decreased from V1 to V4. Compared to BR stimuli, the response to BFR stimuli decreased with increasing eccentricity, specifically within V3 and V4. Taken together, it seems that although the processing of exclusively monocular information decreases from V1 to V4, the processing of binocularly fused information increases from earlier to later visual areas. Our findings suggest the presence of an inhibitory neural mechanism which, depending on the presence of fusion, acts differently on the processing of monocular information.     

Differences in Human Cortical Gene Expression Match the Temporal Properties of Large-Scale Functional Networks

We explore the relationships between the cortex functional organization and genetic expression (as provided by the Allen Human Brain Atlas). Previous work suggests that functional cortical networks (resting state and task based) are organized as two large networks (differentiated by their preferred information processing mode) shaped like two rings. The first ring–Visual-Sensorimotor-Auditory (VSA)–comprises visual, auditory, somatosensory, and motor cortices that process real time world interactions. The second ring–Parieto-Temporo-Frontal (PTF)–comprises parietal, temporal, and frontal regions with networks dedicated to cognitive functions, emotions, biological needs, and internally driven rhythms. We found–with correspondence analysis–that the patterns of expression of the 938 genes most differentially expressed across the cortex organized the cortex into two sets of regions that match the two rings. We confirmed this result using discriminant correspondence analysis by showing that the genetic profiles of cortical regions can reliably predict to what ring these regions belong. We found that several of the proteins–coded by genes that most differentiate the rings–were involved in neuronal information processing such as ionic channels and neurotransmitter release. The systematic study of families of genes revealed specific proteins within families preferentially expressed in each ring. The results showed strong congruence between the preferential expression of subsets of genes, temporal properties of the proteins they code, and the preferred processing modes of the rings. Ionic channels and release-related proteins more expressed in the VSA ring favor temporal precision of fast evoked neural transmission (Sodium channels SCNA1, SCNB1 potassium channel KCNA1, calcium channel CACNA2D2, Synaptotagmin SYT2, Complexin CPLX1, Synaptobrevin VAMP1). Conversely, genes expressed in the PTF ring favor slower, sustained, or rhythmic activation (Sodium channels SCNA3, SCNB3, SCN9A potassium channels KCNF1, KCNG1) and facilitate spontaneous transmitter release (calcium channel CACNA1H, Synaptotagmins SYT5, Complexin CPLX3, and synaptobrevin VAMP2).     

Enhancing oscillations in intracranial electrophysiological recordings with data-driven spatial filters

In invasive electrophysiological recordings, a variety of neural oscillations can be detected across the cortex, with overlap in space and time. This overlap complicates measurement of neural oscillations using standard referencing schemes, like common average or bipolar referencing. Here, we illustrate the effects of spatial mixing on measuring neural oscillations in invasive electrophysiological recordings and demonstrate the benefits of using data-driven referencing schemes in order to improve measurement of neural oscillations. We discuss referencing as the application of a spatial filter. Spatio-spectral decomposition is used to estimate data-driven spatial filters, a computationally fast method which specifically enhances signal-to-noise ratio for oscillations in a frequency band of interest. We show that application of these data-driven spatial filters has benefits for data exploration, investigation of temporal dynamics and assessment of peak frequencies of neural oscillations. We demonstrate multiple use cases, exploring between-participant variability in presence of oscillations, spatial spread and waveform shape of different rhythms as well as narrowband noise removal with the aid of spatial filters. We find high between-participant variability in the presence of neural oscillations, a large variation in spatial spread of individual rhythms and many non-sinusoidal rhythms across the cortex. Improved measurement of cortical rhythms will yield better conditions for establishing links between cortical activity and behavior, as well as bridging scales between the invasive intracranial measurements and noninvasive macroscale scalp measurements.     

Modulation of Force below 1 Hz: Age-Associated Differences and the Effect of Magnified Visual Feedback

Oscillations in force output change in specific frequency bins and have important implications for understanding aging and pathological motor control. Although previous studies have demonstrated that oscillations from 0–1 Hz can be influenced by aging and visuomotor processing, these studies have averaged power within this bandwidth and not examined power in specific frequencies below 1 Hz. The purpose was to determine whether a differential modulation of force below 1 Hz contributes to changes in force control related to manipulation of visual feedback and aging. Ten young adults (25±4 yrs, 5 men) and ten older adults (71±5 yrs, 4 men) were instructed to accurately match a target force at 2% of their maximal isometric force for 35 s with abduction of the index finger. Visual feedback was manipulated by changing the visual angle (0.05°, 0.5°, 1.5°) or removing it after 15 s. Modulation of force below 1 Hz was quantified by examining the absolute and normalized power in seven frequency bins. Removal of visual feedback increased normalized power from 0–0.33 Hz and decreased normalized power from 0.66–1.0 Hz. In contrast, magnification of visual feedback (visual angles of 0.5° and 1.5°) decreased normalized power from 0–0.16 Hz and increased normalized power from 0.66–1.0 Hz. Older adults demonstrated a greater increase in the variability of force with magnification of visual feedback compared with young adults (P = 0.05). Furthermore, older adults exhibited differential force modulation of frequencies below 1 Hz compared with young adults (P<0.05). Specifically, older adults exhibited greater normalized power from 0–0.16 Hz and lesser normalized power from 0.66–0.83 Hz. The changes in force modulation predicted the changes in the variability of force with magnification of visual feedback (R² = 0.80). Our findings indicate that force oscillations below 1 Hz are associated with force control and are modified by aging and visual feedback.     

Encoding of Naturalistic Stimuli by Local Field Potential Spectra in Networks of Excitatory and Inhibitory Neurons

Recordings of local field potentials (LFPs) reveal that the sensory cortex displays rhythmic activity and fluctuations over a wide range of frequencies and amplitudes. Yet, the role of this kind of activity in encoding sensory information remains largely unknown. To understand the rules of translation between the structure of sensory stimuli and the fluctuations of cortical responses, we simulated a sparsely connected network of excitatory and inhibitory neurons modeling a local cortical population, and we determined how the LFPs generated by the network encode information about input stimuli. We first considered simple static and periodic stimuli and then naturalistic input stimuli based on electrophysiological recordings from the thalamus of anesthetized monkeys watching natural movie scenes. We found that the simulated network produced stimulus-related LFP changes that were in striking agreement with the LFPs obtained from the primary visual cortex. Moreover, our results demonstrate that the network encoded static input spike rates into gamma-range oscillations generated by inhibitory–excitatory neural interactions and encoded slow dynamic features of the input into slow LFP fluctuations mediated by stimulus–neural interactions. The model cortical network processed dynamic stimuli with naturalistic temporal structure by using low and high response frequencies as independent communication channels, again in agreement with recent reports from visual cortex responses to naturalistic movies. One potential function of this frequency decomposition into independent information channels operated by the cortical network may be that of enhancing the capacity of the cortical column to encode our complex sensory environment.     

Cell Type-Specific Properties of Subicular GABAergic Currents Shape Hippocampal Output Firing Mode

GABAergic function of the subiculum is central to the regulation of hippocampal output activity. Subicular neuronal networks are indeed under potent control by local inhibition. However, information about the properties of GABAergic currents generated by neurons of this parahippocampal area in normal tissue is still missing. Here, we describe GABA_A receptor (GABA_AR)-mediated phasic and tonic currents generated by principal cells (PCs) and interneurons (INs) of the rat subiculum. We show that in spite of similar synaptic current densities, INs generate spontaneous IPSCs (sIPSCs) that occur less frequently and exhibit smaller charge transfer, thus receiving less synaptic total current than PCs. Further distinction of PCs between intrinsically bursting (IB) and regular-spiking (RS) neurons suggested that sIPSCs generated by the two PC sub-types are likely to be similar. PCs and INs are also controlled by a similar tonic inhibition. However, whereas a comparable tonic current density is found in RS cells and INs, IB neurons are constrained by a greater inhibitory tone. Finally, pharmacological blockade of GABA_AR did not promote functional switch of RS neurons to IB mode, but influenced the bursting propensity of IB cells and released fast spiking activity in INs. Our findings reveal differences in GABAergic currents between PCs and INs as well as within PC sub-types. We propose that GABAergic inhibition may shape hippocampal output activity by providing cell type-specific fine-tuning of subicular excitatory and inhibitory drives.