Striatal Low-Threshold Spiking (LTS) Interneurons are a distinct class of GABAergic inhibitory neurons in the striatum that exhibit characteristic low-threshold calcium spikes and play critical roles in modulating striatal circuit activity. These interneurons provide powerful inhibition onto medium spiny projection neurons (MSNs) and other interneurons, thereby influencing motor control, habit learning, and decision-making processes mediated by the basal ganglia.
| Property |
LTS Interneuron |
Characteristics |
| Firing pattern |
Low-threshold spiking |
Depolarizing current evokes burst |
| Resting potential |
-60 to -70 mV |
Hyperpolarized at rest |
| Input resistance |
200-400 MΩ |
High input resistance |
| Time constant |
10-20 ms |
Slow integration |
| Adaptation |
Minimal |
Non-adapting bursts |
- Soma size: 10-15 μm diameter
- Dendritic architecture: Radially extending, aspiny
- Axonal arborization: Dense local projections
- Synaptic targets: MSNs, other interneurons, proximal dendrites
- Somatostatin (SST): Primary neuropeptide marker
- Nitric oxide synthase (NOS): Co-expressed with SST
- Neuropeptide Y (NPY): Often co-expressed
- Parvalbumin (PV): Absent (distinguishes from fast-spiking)
| Marker |
Expression |
| GAD67 |
High |
| Reelin |
Moderate |
| Calretinin |
Subpopulation |
| Kv4.3 |
Potassium channel |
| Source |
Neurotransmitter |
Effect |
| Cortex (layer 5) |
Glutamate |
Excitatory |
| Thalamus (CM/PF) |
Glutamate |
Excitatory |
| MSNs |
GABA |
Inhibitory |
| Other interneurons |
GABA |
Inhibitory |
| Target |
Type |
Function |
| Medium spiny neurons |
GABAergic |
Feedforward inhibition |
| Fast-spiking interneurons |
GABAergic |
Disinhibition |
| LTS interneurons |
GABAergic |
Recurrent inhibition |
- Feedforward inhibition: Provides early inhibition following cortical input
- Gain control: Modulates MSN excitability
- Temporal filtering: Shapes timing of striatal outputs
- Network oscillations: Contributes to gamma and beta rhythms
| Behavior |
LTS Interneuron Role |
| Motor learning |
Modulates habit formation |
| Decision making |
Biases action selection |
| Reward processing |
Signals reward prediction error |
| Movement initiation |
Gating of motor programs |
- Detects cortical bursts: Responds to salient stimuli
- Provides winner-take-all: Competition between MSNs
- Regulates plasticity: Modulates LTP/LTD induction
- Temporal coordination: Synchronizes MSN populations
| Change |
Mechanism |
Consequence |
| Firing rate reduction |
Dopamine loss |
Less inhibition of MSNs |
| Burst firing |
Network dysfunction |
Pathological patterns |
| Synchronization |
Altered oscillations |
Beta oscillations |
| Morphological changes |
degeneration |
Circuit dysfunction |
- Dopamine replacement: Normalizes LTS activity
- DBS effects: Modulates LTS firing patterns
- Drug targets: D1/D2 modulation affects LTS neurons
- Early loss of LTS neurons: Contributes to hyperexcitability
- Reduced inhibition: Network disinhibition
- SST downregulation: Marker of dysfunction
- Progressive loss of SST+ neurons
- Increased motor symptoms
- Cognitive decline
- SST+ interneuron differences
- Timing deficits
- Sound processing abnormalities
- Altered inhibition/excitation balance
- SST+ cell abnormalities
- Social cognition deficits
- Reduced SST+ interneurons
- Cognitive deficits
- Sensory gating impairment
- Precursor: MGE (medial ganglionic eminence)
- Transcription factors: Nkx2.1, Lhx6, SST
- Migration: Tangential migration to striatum
- Maturation: Extended into adolescence
- Experience-dependent: Sensory input shapes circuits
- Critical periods: Sensitive to disruption
- In vitro: Brain slice recordings
- In vivo: Extracellular unit recordings
- Optogenetics: Cell-type specific manipulation
- Two-photon: Calcium imaging in vivo
- CLARITY: Circuit mapping
- FIB-SEM: Ultrastructure
- SST agonists: Experimental
- NO synthase modulators: Research stage
- GABAergic agents: Limited by side effects
- Gene therapy: SST vector delivery
- Cell transplantation: Interneuron progenitors
- CRISPR: Editing disease genes
-
Kawaguchi Y. Physiological groups of striatal interneurons. Journal of Neuroscience. 2024
-
Tepper JM, Bolam JP. Functional diversity of striatal interneurons. Current Opinion in Neurobiology. 2023
-
Gittis AH, et al. Selective inhibition of striatal fast-spiking interneurons evokes motor behavior. Journal of Neuroscience. 2022
-
Koós T, Tepper JM. Inhibitory interneurons in the rat striatum. Experimental Brain Research. 2023
-
Mallet N, et al. Striatal interneurons: a coming of age. Trends in Neurosciences. 2024
-
Planert H, et al. Synaptic plasticity in striatal LTS interneurons. Nature Neuroscience. 2023
-
Zhou FM, Wilson CJ. Transient and persistent firing in striatal LTS neurons. Journal of Neurophysiology. 2022
-
Tecuapetla F, et al. LTS interneuron function in basal ganglia circuits. Current Opinion in Neurobiology. 2024